Bacterial Pathogenesis · Bacterial Pathogenesis A Molecular Approach Fourth Edition Brenda A....

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BacterialPathogenesis


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BacterialPathogenesis

A Molecular Approach

Fourth Edition

Brenda A. WilsonDepartment of Microbiology

University of Illinois at Urbana-ChampaignUrbana-Champaign, Illinois

Malcolm E. WinklerDepartment of Biology

Indiana UniversityBloomington, Indiana

Brian T. HoInstitute of Structural and Molecular Biology

University College London and Birkbeck, University of LondonLondon, United Kingdom

Washington, DC


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Copyright © 2019 American Society for Microbiology. All rights reserved. No part of this publi-cation may be reproduced or transmitted in whole or in part or reused in any form or by any means, electronic or mechanical, including photocopying and recording, or by any information storage and retrieval system, without permission in writing from the publisher.

Disclaimer: To the best of the publisher’s knowledge, this publication provides information con-cerning the subject matter covered that is accurate as of the date of publication. The publisher is not providing legal, medical, or other professional ser vices. Any reference herein to any specific commercial products, procedures, or ser vices by trade name, trademark, manufacturer, or other wise does not constitute or imply endorsement, recommendation, or favored status by the American Society for Microbiology (ASM). The views and opinions of the author(s) expressed in this publication do not necessarily state or reflect those of ASM, and they shall not be used to advertise or endorse any product.

Library of Congress Cataloging- in- Publication Data

Names: Wilson, Brenda A., author. | Winkler, Malcolm E, author. | Ho, Brian T. (Brian Thomas), author. | Salyers, Abigail A. Bacterial pathogenesis.Title: Bacterial pathogenesis : a molecular approach / Brenda A. Wilson, Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana-Champaign, Illinois, Malcolm E. Winkler, Department of Biology, Indiana University, Bloomington, Indiana, Brian T. Ho, Institute of Structural and Molecular Biology, University College London and Birkbeck, University of London, London, United Kingdom.Description: Fourth edition. | Washington, DC : ASM Press, [2019] | Revised and updated edition of the work originally authored by Abigail Salyers and Dixie Whitt.Identifiers: LCCN 2019017126 (print) | LCCN 2019018854 (ebook) | ISBN 9781555819415 (eBook) | ISBN 9781555819408 (pbk.)Subjects: LCSH: Bacterial diseases— Pathogenesis. | Molecular microbiology.Classification: LCC QR201.B34 (ebook) | LCC QR201 .B34 S24 2019 (print) | DDC 579.3/165— dc23LC rec ord available at https:// lccn . loc . gov / 2019017126

All Rights ReservedPrinted in Canada

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doi:10.1128/9781555819415

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Cover image: Antibiotic (streptomycin) molecules being expelled out of a bacterium through the TolC efflux- pump. 3d rendering. Image courtesy of Juan Gaertner/Science Photo Library, used with permission. Based on Murakami S, Nakashima R, Yamashita E, Yamaguchi A. 2002. Nature 419:587–593.

http://[email protected]


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To Abigail A. Salyers and Dixie D. Whitt

In recognition of their intrepid vision and leadership that

forged the foundation of this fascinating exploration of

the field of bacterial pathogenesis

Herein, their legacy lives on.


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Preface xviiIn Memoriam xixAbout the Authors xxi

CHAPTER 1 The Power of Bacteria 2

Why Are Bacteria So Much in the Public Health Spotlight Nowadays? 3Bacteria, a Formidable Ancient Life Form 4Pressing Current Infectious Disease Issues 6Emerging and Reemerging Infectious Diseases 6Foodborne and Waterborne Infections 7Modern Medicine as a Source of New Diseases 8Postsurgical and Other Wound Infections 9Bioterrorism 10A New Re spect for Prevention 10Surveillance: An Early Warning System 11Making Hospitals Safe for Patients 12And Now for Some Good News: You’ve Got a Bacterial Infection! 12The Helicobacter pylori Revolution 12The Aftermath 13Microbiota Shift Diseases 13A Brave New World of Pathogenesis Research 14The New Age of Genomics 16Insights into Pathogen Evolution 17Modeling the Host- Pathogen Interaction in Experimental Animals 17Correlation Studies 18Selected Readings 18Questions 20

CHAPTER 2 Skin and Mucosa: The First Lines of Defense against Bacterial Infections 22

The Best Defense: Avoid, Reduce, and Prevent Exposure! 23Barriers: Skin and Mucosal Membranes 24The Layers of Cells That Protect the Body 24Normal Microbiota of the Skin and Mucosa 27Defenses of the Skin 31

Contents


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viii • CONTENTS

Defenses of Mucosal Surfaces 32Special Defenses of the Gastrointestinal Tract 34Special Defenses of the Urogenital Tract 36Special Defenses of the Respiratory Tract 36Immune Defenses of the Skin and Mucosa 37Models for Studying Breaches of Barrier Defenses 38Selected Readings 39Questions 39

CHAPTER 3 The Innate Immune System: Always on Guard 40

Triggering Innate Immune Defenses 41Innate Immune Cells That Defend Blood and Tissue 42Neutrophils (PMNs) 42Monocytes, Macrophages, and Dendritic Cells (DCs) 42Granulocytes: Basophils, Mast Cells, and Eosinophils 47Transmigration— How Do Phagocytes Know When and Where to Go? 47Natu ral Killer (NK) Cells 48The Lymphatic System 50How Phagocytes Recognize and Respond to Bacteria 50How Phagocytes Kill Bacteria 54Oxidative Burst in Phagolysosomes 54Autophagy— Another Pathway for the Killing of Intracellular Pathogens 56The Complement Cascade 57Complement Proteins 57Overview of Complement Pathways and Their Function 58Steps in Complement Activation 60Controlling Complement Activation 62Cytokines and Chemokines— Mediators of Immune Responses 63Roles of Cytokines and Chemokines in Directing Innate Immune Responses 63Inflammation and Collateral Damage 65Septic Shock: The Dark Side of the Innate Defenses 66Other Innate Defenses of the Body— Nutritional Immunity 69Selected Readings 70Questions 70

CHAPTER 4 The Adaptive Defenses: Antibodies and Cytotoxic T Cells 72

The Specialists: Adapting to a Par tic u lar Pathogen Challenge 73B Cells: Producers of Antibodies 74The Humoral (Antibody) Immune Response 74Characteristics of Antibodies and Their Diverse Roles in Preventing Infection 74Serum Antibodies 76Secretory Antibodies: Antibodies That Protect Mucosal Surfaces 78Pathogen and Toxin Neutralization by Antibodies 79Affinity and Avidity 80Cytotoxic T Cells, Also Known as Cytotoxic T Lymphocytes (CTLs) 81Cytotoxic T Lymphocytes: Critical Defense against Intracellular Pathogens 81Antigen Pre sen ta tion to the Immune System 82Pro cessing of Protein Antigens by Dendritic Cells 82Interaction between APCs and T Cells: The T- Cell- Dependent Response 84Th-(Th1/Th2/Th17)- Cell- Mediated Immunity 86Production of Antibodies by B Cells 87Links between the Innate and Adaptive Defense Systems 88


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CONTENTS • ix

T- Cell- Independent Antibody Responses 89Mucosal Immunity: IgA/sIgA Antibodies 89Development of the Adaptive Immune System from Infancy to Adulthood 92Adaptive Defense Systems in Nonmammals 93The Dark Side of the Adaptive Defenses: Autoimmune Disease 93Selected Readings 94Questions 94Solving Prob lems in Bacterial Pathogenesis 95

CHAPTER 5 The Microbiota of the Human Body: Microbiomes and Beyond 98

Importance of the Normal Resident Microbial Populations (Microbiota) of the Human Body 99Characterization of the Body’s Microbiota 100Taking a Microbial Census by Using Microbial rRNA Gene Sequence Analy sis 101Characterizing Microbiomes by Using Metagenomic Analy sis 115Beyond the Metagenome 117Overview of the Human Microbiota 123Skin Microbiota 124Oropharyngeal Microbiota 125Microbiota of the Small Intestine and Colon 125Microbiota of the Vaginal Tract 128The Other Microbiota: The Forgotten Eukaryotes 130Selected Readings 130Questions 131Solving Prob lems in Bacterial Pathogenesis 133

CHAPTER 6 Microbes and Disease: Establishing a Connection 134

History and Relevance of Koch’s Postulates 136Early Germ Theory 136Koch’s Postulates: A Set of Criteria Used To Establish a Microbe- Disease Connection 137Challenges to Satisfying Koch’s Postulates 138Easier Said than Done . . . 138The First Postulate: Association of the Microbe with Lesions of the Disease 139The Second Postulate: Isolating the Bacterium in Pure Culture 140The Third Postulate: Showing that the Isolated Bacterium Causes Disease Experimentally in Humans or Animals 141The Fourth Postulate: Reisolating the Bacterium from the Intentionally Infected Animal 143Modern Alternatives To Satisfy Koch’s Postulates 143Detecting the Presence of the Pathogen Only in Diseased Tissues 143Eliminate the Pathogen and Prevent or Cure the Disease 144Comparative Infectious Disease Causation 147The Microbiota Shift Disease Prob lem 147Koch’s Postulates and Pathogenic Microbial Communities 147Keystone Pathogens and Microbial Shift Diseases 147Molecular Koch’s Postulates 149Concepts of Disease 150Va ri e ties of Human- Microbe Interactions 150Views of the Human- Microbe Interaction 150Virulence as a Complex Phenomenon 152Selected Readings 152Questions 153Solving Prob lems in Bacterial Pathogenesis 153


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CHAPTER 7 Mechanisms of Ge ne tic Modification and Exchange: Role in Pathogen Evolution 156

Adapt or Perish 158Acquiring New Virulence Traits by Horizontal Gene Transfer 158Mechanisms of Ge ne tic Change and Diversification 158Spontaneous Mutation 158Phase Variation 159Antigenic Variation 161Horizontal Gene Transfer: Mobile Ge ne tic Ele ments 162Natu ral Transformation 162Conjugation: Plasmids and Transposons 165Phage Transduction 171Control of Horizontal Gene Transfer 171Toxin- Antitoxin Systems— Retaining the Goods 171Restriction- Modification Systems— Bacterial Innate Immunity from Foreign DNA 173CRISPR- Cas Systems— Bacterial Adaptive Immunity from Foreign DNA 173Type 6 Secretion Systems— Bacterial Defense Against Conjugation 174Pathogenicity Islands and Pathogen Evolution 174Properties of Pathogenicity Islands 174Pathogen Evolution in Quantum Leaps 177Selected Readings 178Questions 179Solving Prob lems in Bacterial Pathogenesis 179

CHAPTER 8 Identification of Virulence Factors: Mea sur ing Infectivity and Virulence 182

How Does One Experimentally Mea sure Virulence and Satisfy Koch’s Postulates? 183Animal Models of Infection 184 Human Volunteers 184Nonhuman Animal Models 186Mea sur ing Bacterial Infection in Animal Models 188Ethical Considerations 188Animal Model Basics 188Survival Curve Analy sis and Biophotonic Imaging 189ID50 and LD50 Values 190Competition Assays 191Tissue Culture and Organ Culture Models 192Tissue Culture Models 192Gentamicin Protection Assay for Cell Adhesion and Invasion 193Plaque Assay for Intracellular Survival and Cell- to- Cell Spread 195Fluorescence Microscopy Techniques for Assessing Effects of Pathogens on Host Cells 196Organ Culture Models 196The Continuing Need for Reliable and Plentiful Information about Disease Pathology 197Selected Readings 198Questions 199Solving Prob lems in Bacterial Pathogenesis 200

CHAPTER 9 Identification of Virulence Factors: Molecular Approaches for Bacterial Factors 202

Finding a Needle in a Haystack 204Biochemical Approaches 204Isolation and Purification of Toxic Factors 204Molecular Ge ne tic Approaches 208Screening Using Recombinant Genes 208Reporter Fusions 208

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Mutagenesis Screening 210Genome- wide Sequencing Approaches for Identifying Virulence Genes 214Tn- Seq Technology to Identify In Vivo- Expressed Genes 214RNA- Seq Technology to Identify In Vivo- Expressed Genes 216Comparative Genomic Sequence Analy sis for Identifying Virulence Genes 217Proteomics Approaches for Identifying Virulence Factors 218Protein Microarrays (Proteoarrays) 218In Vivo- Induced Antigen Technology (IVIAT) 218The Importance of Understanding Bacterial Physiology 219Selected Readings 222Questions 223Solving Prob lems in Bacterial Pathogenesis 223

CHAPTER 10 Identification of Virulence Factors: Molecular Approaches for Host Factors 226

Comparative Approaches to Identify Host Factors Required for Infection 227Transgenic Animal Models 228In vivo Imaging of Animals during Infection 231Systems Ge ne tics: Comparative Genomics of the Host Response 231Screening Approaches to Identify Host Factors Required for Infection 235Genome- Wide Screening 235Host Response Profiling to Identify Host Factors Required for Infection 240Transcriptomics 240Proteomics 243Metabolomics 246The Promise and the Caution 247Selected Readings 248Questions 249Solving Prob lems in Bacterial Pathogenesis 249

CHAPTER 11 Bacterial Strategies for Colonization and Survival in the Host 254

What Does Not Kill You Makes You Stronger— Or, a Better Pathogen 255Preinfection 258Survival in the External Environment 258Biofilms 258Motility and Chemotaxis 260Colonization of Host Surfaces 263Penetrating Intact Skin 263Penetrating the Mucin Layer 263Evading the Host’s Innate Immunity 264Nutrient and Iron Acquisition Mechanisms 265Adherence 268Evading the Host Immune Response 275Avoiding Complement and Phagocytosis 277Invasion and Uptake by Host Cells 280Surviving Phagocytosis 281Cell- to- Cell Spread 286Tissue Penetration and Dissemination 288Beyond Virulence Factors 288Selected Readings 289Questions 290Solving Prob lems in Bacterial Pathogenesis 290Special Global Perspective Prob lem: Integrating Concepts in Pathogenesis 291

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CHAPTER 12 Toxins and Other Toxic Virulence Factors 294

Bacterial Toxins 295Transparent Mechanisms, Exciting Applications, Mysterious Purposes 295Toxin Characteristics and Nomenclature 300Nonprotein Toxins 302Peptide and Protein Exotoxins 304Toxic Effector Proteins of Specialized Secretion Systems 312Examples of Toxin- Mediated Diseases 313Diphtheria Toxin 313Clostridial Neurotoxins 319Cholera Toxin 323Toxin- Based Therapeutics and Research Tools 327Immunotoxins 327Selected Readings 329Questions 330Solving Prob lems in Bacterial Pathogenesis 331

CHAPTER 13 Delivery of Virulence Factors 334

Bacterial Secretion Systems and Virulence 335Common Secretory Systems 336The General Secretory (Sec) System 336The Accessory Secretory (Sec) System 336The Cotranslational Signal- Recognition Particle (SRP) System 336The Twin- Arginine Transport (TAT) System 337Secretion Systems Specific to Gram- Negative Bacteria 338Sec- Dependent Secretion Systems 338Sec- Independent Secretion Systems 341Specialized Secretion Systems Specific to Gram- Positive Bacteria 350General Secretory Transporter Systems in Gram- Positive Bacteria 350Cytolysin- Mediated Translocation (CMT) in S. pyogenes (Group A Strep) 351Type 7 Secretion System (T7SS) 352Selected Readings 353Questions 354Solving Prob lems in Bacterial Pathogenesis 355

CHAPTER 14 Virulence Regulation 360

Virulence Gene Regulation 361Mechanisms of Regulation 361Operons, Regulons, and Global Regulators 362Activators and Repressors 362Two- Component Regulatory Systems 364Sigma Factors 368Transcriptional Terminators and Antiterminators 369Regulation of Translation Initiation 372Regulatory Small RNAs 372Bacterial Chromatin 375Responding to Environmental Signals 376Phase Variation and Bistable Switches 376Hypermutability, Intragenomic Recombination, and Positive Se lection 377Coordinate Virulence Regulation 377Quorum Sensing 378Chemotaxis 387Selected Readings 389Questions 389

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Solving Prob lems in Bacterial Pathogenesis 390Special Global Perspective Prob lems: Integrating Concepts in Pathogenesis 395

CHAPTER 15 Antimicrobial Compounds and Their Targets 400

Antimicrobial Compounds: The Safety Net of Modern Medicine 401The Importance of Antimicrobial Compounds 401Avoiding, Reducing, and Preventing Exposure 402Killing versus Inhibiting Growth 404Tests Used To Assess Antibiotics 404Antiseptics and Disinfectants 405Antibiotics 407Characteristics of Antibiotics 407The Pro cess of Antibiotic Discovery 409The Economics of Antibiotic Discovery 413Mechanisms of Antibiotic Action 416Targets of Antibiotic Action 416Cell Wall Synthesis Inhibitors 417Protein Synthesis Inhibitors 422Antibiotics That Target DNA and RNA Synthesis 425Inhibitors of Tetrahydrofolate Biosynthesis 429The Newest Antibiotics 429The Newest Antibiotic Targets 430Strategies for Enhancing Antibiotic Efficacy 431The Continuing Challenge 432Selected Readings 433Questions 434Solving Prob lems in Bacterial Pathogenesis 435

CHAPTER 16 Antibiotic Re sis tance 436

The Dawning of Awareness— Uh, We Have a Prob lem! 437How Did We Get to Where We Are? 438And Now the Really Scary Part . . . 440Emergence and Challenge of Multidrug Re sis tance (MDR) 440Multiple Re sis tance and Ge ne tic Linkage 441Next- Generation MDR Pathogens: The “Superbugs”! 441Mechanisms of Antibiotic Re sis tance 444Overview of Re sis tance Mechanisms 444Re sis tance to Antiseptics and Disinfectants 444Limiting Access of the Antibiotic 445Enzymatic Inactivation of the Antibiotic 446Modification or Protection of the Antibiotic Target 451Failure to Activate an Antibiotic 453Regulation of Re sis tance Genes 454Antibiotic Tolerance and Persister Cells 457Antibiotic Tolerance 457Per sis tence 459Toxin- Antitoxin Systems 459Horizontal Gene Transfer (HGT) of Re sis tance Genes 461Propagating and Maintaining Antibiotic Re sis tance through Selective Pressure and Changes in Fitness 463 Will We Return to the Pre- Antibiotic Era? 464Returning to Status Quo or Moving Forward? 464The Hunt for Alternative Approaches to Antibiotics 466

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Selected Readings 468Questions 469Solving Prob lems in Bacterial Pathogenesis 470Special Global Perspective Prob lems: Integrating Concepts in Pathogenesis 470

CHAPTER 17 Vaccination: A Critical Component of the Modern Medical Armamentarium 476

Vaccines: A Major Health Care Bargain 477What Makes an Ideal Vaccine? 479Immunization Programs 480Barriers to Implementation and Success of Immunization Programs 483The Antivaccination Movement 484Vaccine Success Stories 485Subunit Vaccines 485Conjugate Vaccines 490Vaccine “Less- than- Success” Stories 492A New Age of Vaccine Development: Making Vaccines Better 494Approaches to Enhancing Immunogenicity 494Adjuvants 494Programming Adaptive Immunity 496Targeting Mucosal Immunity 500Storage of Vaccines— Strategies to Increase Shelf Life 504Passive Immunization 504Selected Readings 505Questions 505Solving Prob lems in Bacterial Pathogenesis 508Special Global Perspective Prob lems: Integrating Concepts in Pathogenesis 510

CHAPTER 18 The Gram- Positive Opportunistic Pathogens 514

What Is an Opportunist? 515Characteristics of Gram- Positive Opportunists 516Notable Gram- Positive Opportunists 516Staphylococcus aureus— Commensal Ready for a Fight 516Staphylococcus epidermidis—Accidental Pathogen 524Streptococcus pneumoniae— “Captain of All the Men of Death” 527Clostridium difficile— True Opportunist 534Other Gram- Positive Opportunists 542Selected Readings 543Questions 544Solving Prob lems in Bacterial Pathogenesis 544

CHAPTER 19 The Gram- Negative Opportunistic Pathogens 548

Jumping Over the (Cell) Wall: Gram- Negative Bacteria Can Be Opportunistic Pathogens Too! 549Common Traits of Gram- Negative Opportunists 549The Dark Side of Some Residents of the Human Body 550The Ever- Changing Face of E. coli 550Klebsiella pneumoniae Nosocomial Infections 554Bacteroides fragilis— The Bad Sheep of the Family 555Porphyromonas gingivalis— A Keystone Pathogen 557Environmental Inhabitants Weigh in as Opportunists 558Pseudomonas aeruginosa— A Versatile Opportunist of the Highest Order 558Burkholderia cepacia Complex— P. aeruginosa’s Evil Twin 565

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Acinetobacter baumannii— A Deadly Threat Emerges from the Iraq War 565 Don’t Forget the Arthropods! 567Ehrlichia spp. 567Selected Readings 568Questions 569Solving Prob lems in Bacterial Pathogenesis 569Special Global Perspective Prob lems: Integrating Concepts in Pathogenesis 570

CHAPTER 20 The Changing Roles of Microbiologists in an Age of Bioterrorism and Emerging Diseases 574

When Microbiologists Are Called to the Front Line 575Tracking Down a Bioterrorist 576Unintentional or Deliberate? 577Timing 579Tracing the Source 579Lessons Learned 579The “Top Four” Bioterror Agents 582Bacillus anthracis Spores 582Smallpox 583Yersinia pestis 583Botulinum Neurotoxin 584What If Bioterrorists Hit Us with Something Completely New? 585Biosecurity in a Complex, Dynamic, and Ever- Changing World 585Food Safety and Biosecurity 586The Case for Food Irradiation 587The Future of Biosecurity 589Selected Readings 589Questions 590Solving Prob lems in Bacterial Pathogenesis 591

Glossary 593Index 661

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Cas systems, and transgenic animal models; the roles of se-creted effectors and innate immunity in pathogen clearance and per sis tence; and the escalating challenges of antimicro-bial re sis tance.

As with previous editions, this textbook is written for students, not for professors. Every effort has been made to maintain a student- friendly aspect to the text, which in-cludes minimizing much of the jargon found in the field. This textbook is not intended to cover in detail every patho-gen known to the medical microbiology field. Instead, there is an emphasis on presenting the material based on core under lying princi ples shared among pathogens and general mechanisms used by the pathogens to overcome the host defenses, and then to provide molecular approaches used by researchers to study and combat them. Each of these basic concepts is illustrated through examples using known pathogens. At the end of each chapter students can delve more deeply into the topics covered through study questions, while problem- solving questions help to hone their skills in reading, analyzing, and interpreting data, as well as designing their own experiments. A popu lar feature of the third edition, the research scenarios with realistic data adapted from actual laboratory studies, challenge stu-dents to interpret data and think of new experiments that could be performed to explore solutions to the prob lems presented. The goal of these prob lems is to help the stu-dents develop problem- solving skills and to gain a better understanding of the practical applications of what they are learning from the textbook. We are grateful to many of our colleagues for sharing their expertise with helpful discus-sions and insights that have contributed to the enhance-ment of the educational experience for the students through this means, including sharing a few of their favorite patho-genesis prob lems.

Since the third edition of Bacterial Pathogenesis: A Mo-lecular Approach was written, the field of bacterial pathogenesis has vastly expanded and evolved.

Some areas have been revolutionized by the manner that research is now conducted in this genome era and the wealth of information obtained from modern advanced technologies, while other areas have become obsolete. These changes have necessitated extensive updating and rewriting of many chapters of the textbook. The death of Abigail Salyers and the retirement of Dixie Whitt in 2013 necessitated the recruitment of a new author, Brian Ho, who like the other remaining authors, Brenda Wilson and Malcolm Winkler, comes with significant expertise and re-search experience in modern approaches to studying bacte-rial pathogenesis.

This textbook is intended to be a living book that evolves in response to the constantly changing research landscape of the field of bacterial pathogenesis. True to this mandate, the fourth edition maintains the overall format of the third edition, building on the core foundations and insights of the previous editions, while expanding into new concepts, key modern innovations and cutting- edge research, and new developments in the field. All- new detailed illustrations, for the first time in stunning full color, depict impor tant con-cepts and mechanisms by which bacterial pathogens inter-act with their hosts, other microbes, and their environments, both inside and outside the body. The enormous advances that have been made in next- generation sequencing tech-nologies and functional genomics and multi- omics ap-proaches have necessitated a complete update for several of the chapters. Expanded topics highlight new developments in the areas of microbiomes; comparative and evolutionary genomics; the power of Tn- Seq, RNA- Seq, and gene- editing technologies; the advancing areas of autophagy, CRISPR-

Preface

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xviii • PREFACE

Greg Payne is thanked for his efforts in early development of the textbook and pushing previous editions through and for initiating this edition and bringing Christine and Megan on board. A special thanks also goes to the amaz-ing graphics artist, Patrick Lane, who generated the won-derful diagrams and drawings for most of the figures in the textbook and who was extremely patient during the multiple rounds of edits.

Fi nally, the authors would like to acknowledge how en-joyable it is to work with such a wonderful publisher as ASM Press. The authors are enormously grateful to the editorial staff at ASM Press, particularly Megan Angelini for her unparalleled competence and attention to detail during the entire writing and editing pro cess and Chris-tine Charlip, Director of ASM Press, for her tremendous support and for helping us keep on track. Se nior Editor


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In memoriam of Abigail Ann Salyers, PhDG. William Arends Professor Emerita of Microbiology University of Illinois at Urbana- Champaign (December 24, 1942– November 6, 2013)

An extraordinary, creative microbiologist and fervent advocate for public science literacy, Abigail Salyers was a power ful voice for championing the vast diversity and richness of the microbial world and expanding the realms of microbial ecol-ogy and clinical microbiology to include the varied host environments as diff er-ent microbial ecosystems.

Abigail and her long- time partner in medical microbiology education, Dixie Whitt, were passionate about Bacterial Pathogenesis: A Molecular Approach. The importance of the groundbreaking first and second editions in coalescing the nascent field of bacterial pathogenesis was profound.

The depth of impact of having known and worked with Abigail on the third edition was enormous, and the outcome simply amazing. We are so grateful for her unwavering efforts to stretch our scientific limits, whether by tackling contro-versial topics, probing emerging areas, or shifting paradigms. The result is a col-orful, living chronicle of this dynamic, ever- evolving field that will continue in this fourth edition and beyond.

Abigail, your “BP baby” is safe with us . . .

Abigail A. Salyers 1942–2013

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tions of toxin- producing and extensively drug-resistant bacteria and microbiomes in health and disease.

Malcolm E. Winkler, PhD, is cur-rently a Professor in the Microbiology Section of the Department of Biology and an Adjunct Core Professor in the Department of Molecular and Cellu-lar Biochemistry at Indiana Univer-sity in Bloomington, Indiana. He earned his BA degree in biology (bio phy-sics) at Johns Hopkins University in

Baltimore, Maryland, where he remained for his PhD de-gree in biology (ge ne tics), studying the control of histidine (his) operon metabolic regulation by stringent response in Salmonella enterica serovar Typhimurium in the labora-tory of Professor Philip E. Hartman. He was a Helen Hay Whitney Postdoctoral Fellow in the laboratory of Professor Charles Yanofsky at Stanford University in Stanford, Cali-fornia, USA, where he reported the pausing mechanism in attenuation regulation of the tryptophan (trp) operon and used oligonucleotides to test the trp attenuation model. Thereafter, Dr. Winkler was a tenured faculty member at Northwestern University Medical School in Chicago, Illinois, and the University of Texas Houston Medical School in Houston, Texas, determining the path-way of vitamin B6 biosynthesis in Escherichia coli K-12 and studying the functions of tRNA modification enzymes encoded by complex operons in E. coli. He also worked on the physiological roles of the Hfq RNA chaperone and the posttranscriptional mechanisms that regulate MutHLS methyl- directed mismatch repair proteins in E. coli. Dr. Winkler next worked as a Research Advisor (Director) in antibiotic drug discovery at Eli Lilly and Com pany in Indianapolis, Indiana, where he changed his research

Brenda Anne Wilson, PhD, is cur-rently a Professor of Microbiology and Associate Director of Undergraduate Education in the School of Molecular & Cellular Biology, College of Liberal Arts and Sciences, an Inaugural Pro-fessor in the Carle Illinois College of Medicine, and a Professor of Pathobi-ology in the College of Veterinary

Medicine at the University of Illinois at Urbana- Champaign, Urbana, Illinois. She earned her BA degree in biochemistry and German from Barnard College, Columbia University, New York in 1981. She studied as a DAAD gradu ate fellow in biochemistry at the Ludwig- Maximilians Universität München in Munich, Germany. Dr. Wilson received her PhD degree in chemistry from the Johns Hopkins University in Baltimore, Mary land, where she received the Ernest M. Marks Achievement Award and an AAUW doctoral fellow-ship to study the biosynthesis of β- lactam antibiotics in the laboratory of Craig A. Townsend. She then undertook her NIH postdoctoral fellowship training with R. John Collier in the Department of Microbiology at Harvard Medical School, where she began her studies on bacterial protein toxins. Her first tenured faculty appointment was in the Depart-ment of Biochemistry at Wright State University School of Medicine in Dayton, Ohio. Dr. Wilson’s current research fo-cuses on host- microbe interactions with three main basic science and translational research thrusts. The first is un-derstanding the structure- function, cellular activities, and molecular evolution of bacterial protein toxins and their roles in disease. The second is development of novel post- exposure antitoxin therapeutics and toxin- based thera-peutic cargo- delivery platforms. The third is exploiting comparative and functional genomic technologies to ex-plore the role and co- evolutionary host- microbe interac-

About the Authors

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xxii • ABOUT THE AUTHORS

structure and function of the type 6 secretion system (T6SS) and its effectors in Vibrio cholerae and Pseudomonas aerugi-nosa. Continuing as a postdoc, his research turned toward studying the T6SS and other contact- dependent secretion systems, such as DNA conjugation, in the context of in vivo microbial communities. His current research focuses on un-derstanding how under lying bacterial cell- cell interactions shape larger macroscopic microbial population dynamics and microbial community structure.

program to understanding how the physiology, ge ne tics, and cell biology of the Gram- positive human respiratory pathogen, Streptococcus pneumoniae, contribute to its pathogenesis and possibly reveal vulnerabilities that can be exploited as targets for new antibiotics and vaccines. Dr. Winkler’s laboratory is currently determining the composition, coordination, and chronology of the multiple- protein molecular machines that synthesize the pneumo-coccal peptidoglycan cell wall and the homeostatic and stress pathways that regulate peptidoglycan biosynthesis. Dr. Winkler is a Fellow of the American Acad emy of Micro-biology (AAM) and a Fellow of the American Acad emy for the Advancement of Science (AAAS).

Brian Thomas Ho, PhD, is a Lecturer in Bacteriology at the Institute of Structural and Molecular Biology of the University College London and Birkbeck College, University of Lon-don, United Kingdom. He began his research training as an undergraduate researcher in the laboratory of Nancy Kleckner at Harvard University, where

he studied changes in chromosome dynamics throughout the bacterial cell cycle. He then went on to earn his PhD degree in the laboratory of John J. Mekalanos at Harvard Medical School, where he studied vari ous aspects of the


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661

ABC trans port ers, 446, 447Ablate, 229Abscesses, 65, 517, 518A-B tox ins, 307, 309–313

bind ing and en try into host cells, 311ques tions, 330–331struc tures of, 310

A-B type tox ins, 302Accession num ber, 103Accessory fac tor, 341Accessory se cre tory (Sec) sys tem, 336Accidental path o gen, Staphylococcus epidermidis, 524–527Acetobacter xylinum, cap sule com po si tion, 278Acetylcholine (ACh), 321Acetyltransferases, an ti bi otic in ac ti va tion by, 449Acid-fast stain, 139Acid tol er ance re sponse, 34Acinetobacter, microbiomes of new born in fants, 123Acinetobacter baumannii, 10, 331–332, 549

an ti bi otic re sis tance, 472–474, 567dis eases and breach in de fenses, 550ESKAPE, 440, 566re sis tance mech a nisms in, 443threat emerg ing from Iraq War, 565–567

Acinetobacter baylyi, 163Acinetobacter johnsonii, phy lo ge netic trees, 105Acquired im mune re sponse, 73Acquired im mu nity, 477ActA, 287, 290Actin-based mo til ity, 286Actin fil a ments, vi su al i za tion of, 197Actinobacillus, 291, 292Actinobacteria, 35Activating li gands, 49Activating re cep tors, 49Active im mu ni za tion, 478Acute in fec tion, 78Acute in flam ma tory re sponse, 58Acute phase re sponse, 58Acute re spi ra tory dis tress syn drome (ARDS), 304Acyl-homoserine lac tones, 379, 380

bio syn the sis of, 381

Adaptive de fense sys tems, nonmammals, 93Adaptive im mune re sponse, 73Adaptive im mune sys tem, 41, 92Adaptive im mu nity, 47

CRISPR-Cas sys tem in bac te ria, 173–174, 175dark side of, 80DNA vac cine tech nol ogy, 499–500epi tope-based syn thetic vac cine strat e gies, 498–499or gan isms, 93pro gram ming, 496–500tar get ing den dritic cells and in nate im mune sens ing, 496–498

Adenylate cy clase, 297, 301Adherence

afimbrial adhesins, 274–275bac te rial mech a nisms, 269host and bac te rial sig nal trans duc tion, 275pili (fim briae) of Gram-negative bac te ria, 270–271, 273pili (fim briae) of Gram-positive bac te ria, 273–274pili and fim briae, 268, 270role of, 268

Adherens junc tions, 24, 25Adherent-invasive E. coli (AIEC), 552, 554Adhesins, 268Adhesion fre quency, 194Adjuvants

alu mi num salts, 494–495com bi na tion for mu la tions for vac cines, 499Freund’s, 494im por tance of, 494in cor po rat ing in li po somes, 498li po somes, 496mi cro spheres, 496roles in vac cines, 495triterpenoid-based, 495vac cine de vel op ment, 494–496virosomes, 495–496

Adjuvant Systems (AS), 497ADME (ab sorp tion, dis tri bu tion, me tab o lism and ex cre tion), 409A do main, 302ADP-ribosylation, 312, 314ADP-ribosyltransferase, 311Adsorption, 143

Index


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

662 • INDEX

Adverse event, 483Aerobactin, 554, 555Aerococcus christensenii, phy lo ge netic trees, 105Aerolysin fam ily, 308Aeromonas, mo til ity, 262Aerotaxis, 262Affinity, 80–81Affinity chro ma tog ra phy, pro tein A and pro tein G ap pli ca tions, 523Afimbrial adhesins, 274–275Agent Orange, 9Agglutination, 58Aggregatibacter actinomycetemcomitans, 163, 271Aggregative ad her ence fim briae (AAF), 554Agrobacterium tumefaciens, 165, 278, 347AIDS, 7, 465, 484Alarmins, 53–54, 54Alarmone (p)ppGpp, 459Alaska, Iditarod and diph the ria an ti toxin, 316Allergy, 80Alphaproteobacteria, 107Alpha-toxin, 301, 519Alternative path way, 58, 59, 61, 62Alum, 495Alzheimer’s dis ease, 12Amblyomma americanum, 567Amer i can Medical Association, 433Amer i can Type Culture Collection (ATCC), 8Ames strain of Bacillus anthracis, 580Ames test, 409p-Aminobenzoic acid, 428, 429Aminoglycoside-modifying en zymes, en zy matic in ac ti va tion of,

448, 449Aminoglycosides, 423Ampicillin, evo lu tion of re sis tance, 438Amplicons, 17, 101Anabolism, 125Anergy, 494Animal han dling, zoos and re ha bil i ta tion fa cil i ties, 291–292Animal mod els

ba sics, 188–189biophotonic im ag ing, 189–190blood-curdling, 187com pe ti tion as says, 191eth i cal con sid er ations, 188ex am ples of in fec tion, 228hu man ized trans genic, 230ID50 and LD50 val ues, 190–191im mu no de fi cient trans genic, 228–230mea sur ing bac te rial in fec tion in, 188–191sur vival curve anal y sis, 189–190trans genic, 228–230, 230

Animal mod els of in fec tion, 186hu man vol un teers, 184–186non hu man, 186–188

Annotation, 16Anorexia, 66Anthrax, 10, 138, 396, 590

Ames strain of Bacillus anthracis, 580cip ro flox a cin, 427

Anthrax at tacks, 576Anthrax spores, bioterror agent, 582–583Anthrax toxin, 300, 312, 331, 508Anthrax vi rus, term, 580Anti-adhesion ther apy, 467

Anti-anti-sigma fac tors, 369Antibacterial pep tides, 264–265Antibacterials, 404Antibiotic re sis tance, 6, 10, 11–12, 14

al ter na tive ap proaches to an ti bi ot ics, 466–467an ti bi otic tol er ance, 457, 459aware ness of prob lem, 437–438cost of, 439emer gence and chal lenge of mul ti drug re sis tance (MDR),

440–441evo lu tion of, 438fail ure to ac tive an an ti bi otic, 453–454his tory of, 438–440hor i zon tal gene trans fer of re sis tance genes, 461–463lim it ing ac cess of an ti bi otic, 445–446mech a nisms of, 444–457mod i fi ca tion or pro tec tion of tar get, 451–453mul ti ple re sis tance and ge netic link age, 441next gen er a tion MDR path o gens, 441–444per sis tence, 459prop a gat ing and main tain ing, 463–464Pseudomonas aeruginosa, 562, 564–565reg u la tion of re sis tance genes, 454–457re turn ing to sta tus quo or mov ing for ward, 464–466Staphylococcus au re us, 522–523Streptococcus pneumoniae, 534su per bugs, 441–444tox in-antitoxin (TA) sys tems, 459–460

Antibiotics, 404ac tive ef ux of, 446char ac ter is tics of, 407–409eco nom ics of dis cov ery, 413–416en zy matic in ac ti va tion of, 446–451evo lu tion of re sis tance, 438lim it ing ac cess of, 445–446mech a nisms of ac tion, 408pro cess of dis cov ery, 409–413steps in bio syn the sis of, 418tests to as sess, 404–405time line of dis cov ery, 416

Antibodiesaffi n ity and avid ity, 80–81B cells as pro duc ers of, 74–81char ac ter is tics of, 74, 76or gan isms, 93path o gen and toxic neu tral i za tion by, 79–80se cre tory, 78–79se rum, 76–78struc ture of IgG, sIgA, IgD, and IgE, 75time course of elic i ta tion of, 78

Antibody-dependent cell-me di ated cy to tox ic ity (ADCC), 77Antibody-producing cells, 44Antifungals, 404Antigen(s), 74, 479

in cor po rat ing in li po somes, 498mac ro mo lec u lar, 84pep tide, 82, 84

Antigen-binding re gion (Fab), 74Antigen-binding sites, 76Antigen de liv ery sys tems, 494Antigenic de ter mi nant, 76, 479Antigenic var i a tion, 376

ge netic change, 161–162lipooligosaccharide struc tures in Neisseria meningitidis, 164


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

INDEX • 663

Antigen-presenting cells (APCs), 44, 82in ter ac tion with T cells, 84–86MHC I, MHC II, and CD1 path ways, 83

Anti-inflammatory cy to kines, 65Antimicrobial com pounds

avoid ing, re duc ing and pre vent ing ex po sure, 402–403

im por tance of, 401–402kill ing ver sus in hib it ing growth, 404search for new, 411

Antimicrobial pep tides, 34, 93Antimicrobial pep tide sen sor Aps reg u la tory sys tem,

Staphylococcus epidermidis, 526Antiporters, 446, 447Antisense sRNAs, 372, 374Antiseptics, 401, 405–407, 444Anti-sigma fac tors, 369Antitermination fac tors, 369Antiterminators, mech a nism, 371Antitoxin, 204, 315Antivaccination move ment, 484–485

herd im mu nity, 485im pact of, 484re view of vac cine side ef ects, 486–487

Antivirals, 404Apical sur face, 25, 192Apoptosis, 49, 81Apoptotic bod ies, 49ARDB (Antibiotic Resistance Genes Database), 441Arthropod vec tors, 482AS01, 497AS02, 497AS03, 497AS04, 497ASO3, 495Atg12, 56Atg16, 56Atg5, 56Atherosclerosis, 13, 135, 139ATR-binding cas sette (ABC) trans porter, 341Attachment (att) site, 462Attenuation, 369Augmenters, 431Augmentin, 431, 435Aum Shinrikyo, 576Autoclaving, 403Autoimmune dis ease, 93Autoimmune re ac tions, 74Autoimmunity, 74, 80Autoinducer-2 (AI-2), 382Autoinducing pep tides, pro cess ing of, 382Autolysins, 419Autolysosome, 57Autophage, 56Autophagolysosome, 56Autophagosome, 56, 57Autophagy, kill ing in tra cel lu lar path o gens, 56, 57Autophagy-related pro tein Atg8 (LC3), 56Autotransporter, 338Auxiliary cells, 44Avery, Oswald, 163, 527Avidity, 80–81Azithromycin, 424, 425Azospirillum, mo til ity, 262

Azotobacter vinelandii, cap sule com po si tion, 278AZT, 184

Bacillales, 123Bacillus spp.

biofilm, 259sur vival, 258

Bacillus anthracis, 10, 234, 301, 396, 576Ames strain of, 580cap sule com po si tion, 278iso lat ing, 140, 141life cy cle of, 138spores as bioterror agent, 582–583

Bacillus Calmette-Guérin (BCG) vac cine, 229Bacillus ce re us, bac te rio phage ther apy, 466Bacillus megaterium, cap sule com po si tion, 278Bacillus subtilis, 141, 391

es cap ing phagosome, 281quo rum-sensing autoinducers, 379re pres sion of tryp to phan me tab o lism gene, 373

Bacitracin, 418, 421, 422Bacteria

16S rRNA gene-based tax o nom i cal iden ti fi ca tion of, 101, 104, 106–107

adap tive im mu nity, 173–174, 175an cient life form, 4–5cap sule com po si tion, 278cell-to-cell spread, 286–288col o ni za tion of host sur faces, 263–275de tec tion by 16S rRNA gene am pli fi ca tion by PCR, 102dis eases, 13mech a nisms for col o ni za tion and sur vival in host, 256mech a nisms pre vent ing ox i da tive burst, 286mo til ity and che mo taxis, 260–263opsonization of, 60phago cytes kill ing, 54–56phago cytes rec og niz ing and re spond ing to, 50–54pub lic health, 3–4se lect agents and tox ins, 578sur faces of Gram-negative and Gram-positive, 15–16tis sue pen e tra tion and dis sem i na tion, 288vi su al i za tion of in tra cel lu lar, 197

Bacterial cul ture su per na tants, iden ti fy ing vir u lence fac tors, 205Bacterial ge no mics, new drug tar gets by ex ploit ing, 412–413Bacterial growth, model of, 257Bacterial in fec tion

anal y sis of prob lem, 570–572, 573an i mal han dling, 291–292preinfection, 258–263stages of, 257

Bacterial in ter fer ence, staph y lo cocci, 386, 387Bacterial lu cif er ase (lux), 231Bacterial men in gi tis, power of cap sules, 278–279Bacterial path o gen e sis, 204, 223–225Bacterial per sis tence, 459Bacterial phys i ol ogy, un der stand ing, 219, 222Bacterial se cre tion sys tems

sum mary of, 339–340vir u lence and, 335–336

Bacterial tox in(s)char ac ter is tics and no men cla ture, 300–302en do tox ins, 302–304mech a nisms and ap pli ca tions, 295–296, 300mycolactone tox ins, 304


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

664 • INDEX

Bacterial tox in(s) (continued )non pro tein tox ins, 302–304pep tide and pro tein exo tox ins, 304–313prop er ties of se lected, 297–300toxic ef ec tor pro teins, 313

Bacterial vag i no sis, 14, 106Bactericidal, 404Bacteriocins, 28Bacteriolysin ther apy, 466Bacteriophage (δ-phage), 315Bacteriophages, 171Bacteriophage ther apy, 466Bacteriostatic, 404Bacteroides sp., 35, 126, 127Bacteroides fragilis, 288–289, 549

dis eases and breach in de fenses, 550en tero toxi genic B. fragilis, 555Gram-negative op por tun ist, 555–557model of en tero toxi genic B. fragilis-mediated co li tis and

tu mor i gen e sis, 556nonenterotoxigenic B. fragilis, 555, 557

Bacteroidetes, 35, 107, 126, 127Bands, 48Barcodes, 109Barrier de fenses

con se quences of breach ing, 32handwashing, 30–31mod els for study ing breaches of, 38–39see al so Skin and mu co sa

Bartonella ge nus, 147Bartonella bacilliformis, 147Bartonella henselae, 147Bartonella quintana, 147Bartonella vinsonii, 147Basal body, 260Basal lam ina, 25, 26Basal sur faces, 192Base-pairing sRNAs, 372, 374Basolateral sur face, 25Basophils, 42, 47, 78B cell epi topes, 82B cell re cep tor (BCR), 87B cells, 73

or gan isms, 93pro duc ers of an ti bod ies, 74–81pro duc tion of an ti bod ies by, 87–88

Bedaquiline, 429, 430Bel mont Report, 184Beta-toxin, 301Biased ran dom walk, 263Bifidobacteria, 35, 100, 542Bile salts, 35Binary toxin (CDT), 540Bioactive drug can di dates, metabologenomics dis cov ery

ap proach, 414Bioavailability, 407Biofilm(s), 10, 258–260

de vel op men tal life cy cle of, 259ef ects on im mune eva sion in Staphylococcus epidermidis, 524steps in for ma tion, 524

Bioinformatics, 101, 103Biological and Toxins Weapons Convention (BWC or BTWC), 576Biological threats, sources of, 577Biological war fare, con cept of, 575–576

Bioluminescence, 231, 383Biomarkers, 245Biophotonic im ag ing, 188–190, 232Biosecurity, 585

ev er-changing world, 585–586food safety and, 586–589fu ture of, 589

Bioterror agentsBacillus anthracis spores, 582–583bot u li num neu ro toxin, 584–585small pox, 583Yersinia pestis, 583–584

Bioterrorism, 6, 8, 10con cept of, 575hu man cost of, 586les sons learned, 579–582threat of, 579

Bioterrorist(s)tim ing, 579trac ing the source, 579track ing down, 576–579un in ten tional or de lib er ate, 577, 579

Biothreats, 576hu man cost of, 586postal work ers and, 581prop a ga tion of mis in for ma tion, 580

Biowarfare, threat of, 579Bistable switches, 376–377Black Death, Yersinia pestis, 50, 583–584Blackhead, 28Blood clot ting, 67B lym pho cytes (B cells), 74Boiling, 403Bordetella, 367Bordetella tra cheal cy to toxin (TCT), 303Bordetella per tus sis, 37

Bvg sys tem, 390im pact of vac ci na tion pro gram on global phy log eny of, 489phase var i a tion, 160re spi ra tory tract, 37

Borrelia burgdorferi, 16, 95–96, 304, 510, 567Botox, 321, 322Botox craze, 322Botulinum neu ro toxin (BoNT), 10, 296, 310, 320–322

ac tion at mo tor neu ron syn apse, 324bioterror agent, 584–585struc ture of, 323

Botulinum toxin, 591Botulism, 319–320Bradykinin, 65Broad spec trum of ac tiv ity, 407Bronchial-associated lym phoid tis sue (BALT), 38, 90Brucella spp., 180, 181Brucella abortus, fac ul ta tive path o gen, 282, 284, 285Brucellosis, 180Bt (Bacillus thuringiensis) tox ins, 329Buboes, 50Bubonic plague, 50, 584Bull’s-eye rash, 95Bundle-forming pili (Bfp), 551Burkholderia cenocepacia, 271, 549

dis eases and breach in de fenses, 550pneu mo nia, 565

Burkholderia cepacia, 9, 37


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

INDEX • 665

Burkholderia cepacia com plex, 565Burkholderia dolosa, 566Burkholderia mal lei, 576Burkholderia pseudomallei, 251–252Buruli ul cer, 304

C2, 61C2a, 61C2b, 61C3a, 59C3b, 59, 60C3b re cep tors, 60C3 convertase (C2aC4b), 58, 61C3 convertase C3bBb, 62C4, 61C4a, 61C4b, 61C4b-binding pro tein (C4BP), 63C5a, 59C5b, 59Caenorhabditis elegans, 17, 38, 186Calcium-calmodulin-dependent ad e nyl ate

cy clase (Cya), 344Calcium mo bi li za tion, 196Calprotectin, 44, 69Campylobacter, 7, 11, 34, 429Campylobacter jejuni, 163, 165, 356, 435

cell cul ture as says, 195or gan cul ture model, 197

Cancer, 12, 135, 147che mo ther apy, 8stom ach, 6

Candida albicans, 31Capsules, 62, 277, 278–279Capture ELISA, 143, 145Carbapenems, 417, 419CARD (Comprehensive Antibiotic Resistance Database), 441Cardiotoxin, 301Cardiovascular dis ease, 135Caries, 148Carrier state, 139CARVER+Shock, 587Caspase-1, 52Catabolism, 125Catabolite con trol pro tein E (CcpE), 364Catechols, 266Cathelicidins, 34Cationic an ti mi cro bial pep tides, 44ccRNA (CRISPR RNA), 238CD1 mol e cules, 84CD1 path ways, 83CD4 mol e cules, 85CD8 mol e cules, 84CD14, 51CD35 (com ple ment re cep tor 1, CR1), 63CD46 (mem brane co fac tor pro tein), 63CD55 (com ple ment de cay-accelerating fac tor, DAF), 63CD59 (MAC-inhibitory pro tein, MAC–IP)), 63CDC (cho les ter ol-dependent cy to ly sin) fam ily, 308Cdc42, 540Cell-to-cell spread, 195, 286–288Cellular rec og ni tion, LPS through Toll-like re cep tor, 53Cell wall com po nents, 300Cell wall hy dro lases, 531

Cell wall syn the sis in hib i tors, 417–422bac i tra cin, 421, 422fosfomycin, 421gly co pep tides, 420–421β-lactam an ti bi ot ics, 417–420

Centers for Disease Control and Prevention (CDC), 4, 9, 153, 154, 416, 572, 578, 581, 582, 591

Central ner vous sys tem (CNS), 435Cephalosporins, 417, 418, 419

evo lu tion of re sis tance, 438re sis tance, 463

Cerebral palsy, 13Cervical can cer, 12, 147Chaperones, 273Chaperone-usher sys tem, 271Chelocardin, 424Chemoattractants, 263, 387Chemokines, 47, 88

ac tiv i ties, 45–46char ac ter is tics and func tions of, 43me di a tors of im mune re sponses, 63–65roles of, 48

Chemorepellents, 387Chemotaxis, 47, 262, 387–389Chlamydia, 195, 280, 282, 283Chlamydia trachomatis, 128, 218, 220Chlamydophila pneumoniae, 139–140, 187

ath ero scle ro sis, 139heart dis ease and, 142–143im mu no his to chem is try and im mu no flu o res cence

mi cros copy, 144Chlamydophila psittaci, re spi ra tory tract, 37Chloramphenicol, evo lu tion of re sis tance, 438Chloramphenicol acetyltransferases,

en zy matic in ac ti va tion of, 448Chlorination, 402Chloroplasts, 5Cholera, 136, 141, 146, 150, 327, 483Cholera toxin (CT), 90, 301, 310, 323, 325–327, 502

chol era ep i dem ics, 326, 327mech a nism of di ar rhea me di ated by, 325, 327oral re hy dra tion ther apy (ORT), 327Vibrio cholerae, 323, 325

Choline-binding pro teins (CBPs), 529Chromogenic sub strates, 208Cilia, 36Ciliary dys ki ne sia, 560Ciliated co lum nar cells, 36Cipro, 427Ciprofloxacin, 427

evo lu tion of re sis tance, 438struc ture of, 427

Class 1 ma jor his to com pat i bil ity com plex (MHC I), 49–50Classical com ple ment path way, 59, 60–61Clavulanic acid, 431, 448Clindamycin, 425Clinical & Laboratory Standards Institute (CLSI), 440Cloned pro teins, 206Clostridial neu ro tox ins, 297

bot u li num neu ro toxin (BoNT), 320–322bot u lism, 319–320dif er ent tox ins, same mech a nism, 322–323tet a nus, 322

Clostridial tox ins, 297


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

666 • INDEX

Clostridium spp., 35biofilm 259co lon microbiota, 126path o ge nic ity is lands, 177small in tes tine microbiota, 125sur vival, 258

Clostridium bot u li num, 10, 355, 395, 435, 577path o ge nic ity is lands, 177pro tein toxin by, 296

Clostridium dif cile, 6, 99, 128, 132, 515an ti bi ot ics, nor mal gut microbiota and risk of in fec tion, 535ef ects of tox ins on G pro teins, 539model for ac qui si tion of in fec tion, 536as op por tun ist path o gen, 534–542pre ven tion and treat ment of in fec tion, 540, 542pseudomembranous co li tis, 535steps in de vel op ment of in fec tion and pseudomembranous

co li tis, 538tox ins by, 539, 541vir u lence fac tors, 537, 540

Clostridium equiniae, 355–356, 395, 435Clostridium perfringens, 393, 509–510Clostridium perfringens α-toxin, 309Clostridium tetani, 177, 301Clumping fac tor, 520Coagulase, 516Coagulation sys tem, 67Coccidioides immitis, re spi ra tory tract, 37COGs (Clusters of Orthologous Groups), 103Cohn, Fer di nand, 141Cohort, 185Cold War, 576Colibactin, 555Colicin A, 307Colicin fam ily, 308Colicin Ia, 307Coliforms, 402Colitis, en tero toxi genic Bacteroides fragilis, 555Collaborative Cross (CC) mice, 233Collagenases, 288Collagens, 25, 26Collectins, 58Colon, microbiota, 125–126, 128Colonization of host sur fac es

ad her ence, 268–275evad ing the host’s in nate im mu nity, 264–265nu tri tion and iron ac qui si tion, 265–268pen e trat ing in tact skin, 263pen e trat ing the mu cin layer, 263–264

Colony-forming units (CFUs), 188, 194Columnar ep i the lium, 26Combinatorial chem is try, 410Comedo, 28Commensal bac te ria, skin in fec tion with, 28Commensal microbiota, 28Common Rule, 184Community-acquired meth i cil lin-resistant S. au re us (CA-MRSA),

355, 470, 509, 544–545Competent, 163Competition as says, 191Competitive in dex (CI), 191, 200Complement, avoid ing, and phago cy to sis, 277–278, 280Complement ac ti va tion, 58, 60–63Complementary reg u la tory RNAs, 374

Complement cas cade, 57–63com ple ment path ways and func tion, 58–60com ple ment pro teins, 57–58con trol ling com ple ment ac ti va tion, 62–63main steps in ac ti va tion, 59steps in com ple ment ac ti va tion, 60–62

Complement sys tem, 42, 43, 47, 57Complex trait anal y sis (CTA), 231Concatenated, 115Conduction heat ing, 403Congenital ru bella syn drome, mor bid ity be fore and af ter

vac cines, 488Conjugate vac cine, 89, 490Conjugation, 165, 461

plas mids, 165–167, 169, 461, 462, 464trans po sons, 165–167, 169, 462, 463, 464

Conjugative trans po si tion, 167, 168Cons tant re gion (Fc), 74Contigs, 109Continuous epi topes, 76, 480Coordinate reg u la tion, 362Coordinate reg u la tion of vir u lence, 377–378Core ge nome, 516Coriobacterineae, microbiomes of new born in fants, 123Coronary ar tery dis ease, oral bac te ria and, 558Correlation stud ies, 18Corynbacterium diphtheriae, reg u la tion of DT ex pres sion, 317Corynebacterineae, microbiomes of new born in fants, 123Corynebacterium, skin microbiota, 124Corynebacterium diphtheriae, 171, 204, 391, 481

diph the ria toxin (DT), 296re spi ra tory tract, 37

Cosmetic bot u lism, 320, 321, 322Cotranslational sig nal-recognition par ti cle (SRP) sys tem, 336–337Coverage, 109Cowpox vac cine, 477, 478Coxiella, 280, 282, 283Coxiella burnetii, 37, 282CpG ol i go nu cle o tides, 497CpG-rich DNA, 51C-re ac tive pro tein (CRP), 65CRISPR-Cas sys tems, 173–174, 175, 237, 527Crohn’s dis ease, 13, 128Crossbreeding, 233Cryptosporidium, 7Crystal tox ins, 329Crystal vi o let biofilm as say, 571, 572Cry tox ins, 329Cuboidal ep i the lium, 26Cystic fi bro sis, 260, 558

prev a lence of re spi ra tory bac te ria in lungs, 562Pseudomonas aeruginosa and neu tro phils, 561trans mis sion of Burkholderia dolosa among pa tients, 566

Cystic fi bro sis trans mem brane con duc tance reg u la tor (CFTR), 325, 560

Cytokines, 47, 88ac tiv i ties, 45–46char ac ter is tics and func tions of, 43ef ects on re sponses to in fec tion, 66me di a tors of im mune re sponses, 63–65roles of, 48

Cytokine tech nol ogy, 497Cytolethal dis tend ing toxin (CDT), 551Cytolysin, 306


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

INDEX • 667

Cytolysin A (ClyA), 307, 308Cytolysin-mediated trans lo ca tion (CMT), 340, 351Cytoplasm, 287Cytoplasmic mem brane, an ti bi otic up take across, 445–446Cytosol, 57Cytotoxic nec ro tiz ing fac tor 1 (CNF1), 554Cytotoxic nec ro tiz ing fac tors (CNFs), 312–313, 551Cytotoxic T cells, 81Cytotoxic T lym pho cytes (CTLs), 73, 81Cytoxic nec ro tiz ing fac tors, 297

Dalfopristin, 432Danio rerio, 17Daptomycin

evo lu tion of re sis tance, 438struc ture of, 420

Databases, 103–104DDBJ (DNA Data Bank of Japan), 103Decay-accelerating fac tor (DAF), 187Deconvolution, 411Defense, bac te rial in fec tions, 23–24Defensins, 27, 34, 264Deltaproteobacteria, 107Delta-toxin, 301Dendritic cells (DCs), 37, 42, 73

char ac ter is tics and func tions, 43pro cess ing of pro tein an ti gens by, 82, 84

Dental plaque, 148, 511Deoxyribonucleases (DN ases), 288Department of Homeland Security (DHS), 572, 591Derivative toxin, 321Dermis, 24, 25Dermonecrotic tox ins, 297Desmosomes, 24, 25Desquamation, 32Dialister invisus, phy lo ge netic trees, 105Diapedesis, 47Diarrhea

chol era tox in-mediated, 325, 327mo lec u lar ba sis of chol era tox in-mediated, 328rab bit il eal loop model of, 38

Diarylquinoline, 429Dichelobacter nodosus, 176, 271Dictyostelium, 93Diferential tox ic ity, 407Difusely ad her ence E. coli (DAEC), 552, 554Digestive en zymes, 35Digitonin, 3453,5-Dimethylpyrazin-2-ol (DPO), 379, 381Diphthamide, 312Diphtheria, 79, 314–315, 483, 505

im mu ni za tion pro gram, 481mor bid ity be fore and af ter vac cines, 488time lines and im pact of vac cine, 478

Diphtheria an ti toxin, dog Balto and Iditarod, 316Diphtheria toxin (DT), 79, 296, 297, 310, 313–319, 331, 508

diph the ria, 314–315diph the ria an ti toxin, 315diph the ria vac cine, 315dog Balto and Iditarod, 316mech a nism of ac tion, 317–319pro duc tion, 315, 317

Diphtheria tox in-mediated ab la tion, lym phatic en do the lial cells, 229Diphtheria toxin re pres sor (DtxR), 317

Diphthine, 318Direct as so ci a tion, 234Direct ELISA, 143, 145Discontinuous epi topes, 76, 480Disease pa thol ogy, need for, 197–198Diseases

hu man-microbe in ter ac tions, 150, 152vir u lence phe nom e non, 152

Disinfectants, 401, 405–407mode of kill ing, 407re sis tance to, 444

Disseminated in tra vas cu lar co ag u la tion (DIC), 67, 68, 304Diversification, mech a nisms of ge netic change and, 158–162Diversity Outbred (DO) mice, 233DNA (de oxy ri bo nu cleic ac id)

DNA da ta bases, 16in ver tase, 159, 161mech a nism of trans po si tion, 170meth yl ase, 173nat u ral trans for ma tion, 167se quenc ing tech nol ogy, 16trans fer mech a nism, 168

DNA-uptake se quences (DUS), 163DNA vac cines, 499, 505–506DNA vac cine tech nol ogy, 499–500, 506Donor, 165, 347Donor cell, 163Dormancy, 459Dot blot, 569Double-blind pro to col, 415Doxycycline, 423, 424Drosophila, 38, 235Drosophila melanogaster, 17–18, 93Drug dis cov ery, time lines and risks as so ci ated with, 416Druggable, 412DTaP vac cine

diph the ria, tet a nus and whoop ing cough, 485rec om mended im mu ni za tion sched ule, 491

DT/Td tox oid, side ef ect re view, 486–487DtxR, 364Dual-use agents, 577Dual-use re search of con cern (DURC), 577Dysbiosis, 128Dysentery, 115, 116, 551

Ebola pan demic, 581, 585Edema fac tor (EF), 310Edible vac cines, 502–503Efector pro teins, 313

de tec tion of trans lo cated Elk/NLS-tagged, 346frac tion ation and im mu no blot ting, 345

Efector-reporter strat egy, trans lo cated Yop pro teins, 345Efux pumps, 446, 447eggNOG (evo lu tion ary ge ne al ogy of genes: Non-supervised

Orthologous Groups), 103Ehrlichia spp., 549, 567Ehrlichia chaffeensis, 549, 550, 567Ehrlichia ewingii, 549Electron beams, 403, 587Elimination, 480Elongation fac tor-2 (EF-2), 312EMBL ENA (Eu ro pean Molecular Biology Laboratory Eu ro pean

Nucleotide Archive), 103Emerging in fec tious dis eases, 4, 6–7


IP: 54.70.40.11

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668 • INDEX

Endemic, 482Endocarditis, 261Endocytosis, 312Endoflagella, 262Endosome, 312Endospores, 258Endosymbionts, 5Endothelial cells, 50Endothelium, 24, 25Endotoxic shock, 302Endotoxins, 300, 303Enteroaggregative E. coli (EAEC), 552, 554Enterobacter spp., ESKAPE, 440Enterobacteria, 35Enterococcus sp. 35

co lon microbiota, 126Synercid, 432

Enterococcus casseliflavus, phy lo ge netic trees, 105Enterococcus faecalis, op por tun ists, 288–289Enterococcus faecium, 542–543

ESKAPE, 440mem brane al ter ations, 445

Enterocyte at tach ment and ef ace ment (EAE), 551Enterohemorrhagic E. coli (EHEC), 552, 553Enteroinvasive strains of E. coli (EIEC), 551, 552Enteropathogenic E. coli (EPEC), 376Enteropathogenic strains of E. coli (EPEC), 551, 552, 553Enterotoxigenic E. coli (ETEC), 551, 552Enterotoxin, 301, 555Entrez, 103Environmental Protection Agency (EPA), 592Enzyme-linked im mu no sor bent as say (ELISA), 143

cap ture or sand wich ELISA, 143di rect ELISA, 143in di rect ELISA, 143path o gen de tec tion, 145

Eosinophils, 42, 47EPEC ad her ence fac tor (EAF), 553Epidemic, 483Epidemic dis eases, 483

chol era, 326, 327Epidemiology, 11, 146Epidermis, 24, 25Epithelia, 24Epithelial cells, types of, 26Epitope, 76, 479, 480Epitope-based syn thetic vac cine strat e gies, 498–499, 500Epitope-based tar get ing sig nals, 498Epizootic, 482Epsilonproteobacteria, 107Epsilon-toxin, 301Eradication, 480erm (RNA meth yl ase genes), 454Erythema mi grans, 95Erythromycin, 424, 438Eschar, 582Escherichia, 35Escherichia coli, 34, 101, 106, 394, 549

ad her ence mech a nism, 269ad her ent-invasive E. coli (AIEC), 552, 554aminoglycoside an ti bi ot ics, 434antiterminator, 371cap sule com po si tion, 278che mo taxis in, 388

chlo ri na tion, 402co lon microbiota, 126dif usely ad her ent E. coli (DAEC), 552, 554dis eases and breach in de fenses, 550enteroaggregative E. coli (EAEC), 552, 554enterohemorrhagic E. coli (EHEC), 552, 553enteroinvasive E. coli (EIEC), 551, 552en tero patho genic E. coli (EPEC), 551, 552, 553en tero toxi genic E. coli (ETEC), 551, 552ev er-changing face of, 550–554mo til ity, 262neo na tal men in gi tis-causing E. coli (NMEC), 553–554path o ge nic ity is lands, 176, 177phy lo ge netic trees, 105pili, 270–271reg u la tion of lac op eron, 363riboswitches, 373RNA-seq, 118sigma fac tors and func tions in, 368uropathogenic E. coli (UPEC), 552, 553virotypes of, 552, 569virotyping of, 550–551

Escherichia coli O157:H7, 7, 11ESKAPE, 440, 562, 566Eubacterium, 35Eukaryotes, 5, 130Eu ro pean Committee on Antimicrobial Susceptibility Testing

(EUCAST), 440Exfoliation, 553Exfoliative tox ins (ETs), 519Exoenzymes, 298Exotoxin, 300Exotoxin A (ExoA), 561, 564Experimental an i mals, mod el ing host-pathogen in ter ac tion, 17–18ExPortal, 350Extended-spectrum β-lactamases (ESBLs), 448Extensively drug re sis tant (XDR), 441Extracellular ma trix (ECM), 25, 26, 192Extracellular po ly sac cha ride (EPS), 258Extracellular pro teins, 298Extravasation, 47

F (fer til i ty)-factors, 166–167F′ (“F prime”) fac tor, 167Factor B, 62Factor H, 62Facultative in tra cel lu lar path o gens, 282, 283, 284, 285Fc re cep tors, 60Fecal microbiota trans plan ta tion (FMT), 542Female uro gen i tal tracts, 36Fenton re ac tion, 56Ferric up take re pres sor (Fur), 364Ferritin, 266Fever, 66Fibrinolysis, 67Fibrinolytic sys tem, staphylokinase ac ti va tion of, 519Fibronectin-binding pro tein (FnBP), 522Fibronectins, 25, 26Ficolins (FCNs), 58Filament, 260Filamentous hem ag glu ti nin (FHA), 485Filifactor alocis, 148Fimbria, 268Fimbriae, 268, 488


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

INDEX • 669

Firefly lu cif er ase, 231Firmicutes, 104, 107, 126, 127Flagella, 260Flagellar as sem bly, injectisome and, 343Flagellin, 51, 260Flavohemoglobin, 286Fluorescein iso thio cy a nate, 196Fluorescence-activated cell sort ing (FACS), 216Fluorescence mi cros copy tech niques, 196Fluorescence res o nance en ergy trans fer (FRET), 346Fluoroquinolones, 427–429Follicles, 90Food and Drug Administration (FDA), 11, 35, 440, 483Foodborne in fec tious, 6, 7–8Food bot u lism, 320Food ir ra di a tion, 587–589

his tory of, 588mea sur ing, 588tech nol o gies, 587tech nol ogy, 590–591

Food safe tybio se cu rity and, 586–589food ir ra di a tion, 587–589

Footnet, 11Fosfomycin, 418, 421Fragipain (Fpn), 555Francisella tularensis, 201Freeze-drying, 504Freund’s com plete ad ju vant, 494Freund’s in com plete ad ju vant, 494Fur (fer ric up take reg u la tor), 317Fura-2, 196Furanosyl bo rate di es ter, 379Furin, 310Fusobacteria, 35, 107Fusobacterium nucleatum, 125, 133, 148, 511, 560

Galectin-8, 56Gamma (γ) rays, 403Gammaproteobacteria, 107Gamma rays, 587Gamma-toxin, 301Gardnerella vaginalis, 104, 105, 106, 128Gar field, James A., 29Gas chro ma tog ra phy (GC), 120Gastric ul cers, 13

elim i nat ing path o gens, 144, 146–147old dogma vs. new model, 145pro posed for ma tion mech a nism for H. py lo ri, 280

Gastrointestinal-associated lym phoid tis sue (GALT), 38, 90, 91, 92Gastrointestinal tract

bac te ria and quan ti ties, 35de fenses of, 34–36

GenBank, 103Gene con ver sion, 161Gene du pli ca tion and am pli fi ca tion (GDA), 377Gene ed it ing, 235, 237Generalized trans duc ing phages, 171Ge ne ral se cre tory (Sec) sys tem, 336, 337, 339Ge ne ral se cre tory trans porter sys tem, Gram-positive bac te ria, 350–351Gene se quence anal y sis, mi cro bial rRNA, 101, 104, 106–115Gene si lenc ing, 235Genetic ab la tion, 229Genetical ge no mics, 231

Genetic change and di ver si fi ca tionan ti genic var i a tion, 161–162mech a nisms of, 158–162phase var i a tion, 159–161spon ta ne ous mu ta tion, 158–159

Geneva Protocol, 576Genome ed it ing, CRISPR-Cas9-mediated, 238Genome plas tic ity, 258Genome se quence, 16Genome-wide as so ci a tion stud ies (GWAS), 234–235Genome-wide screen ing, 235–240Genome-wide se quenc ing

com par a tive ge no mic se quence anal y sis, 217–218iden ti fy ing vir u lence genes, 214–218RNA-Seq tech nol ogy, 216Tn-Seq tech nol ogy, 214–216

Genomic is lands (GIs), 174, 180Genomic plas tic ity, 377Genomics, 101

com par a tive, of host re sponse, 231, 233–235new age of, 16–17

Genomics-based dis cov ery, 412Genomic se quence anal y sis

com par a tive for iden ti fy ing vir u lence genes, 217–218iden ti fy ing vir u lence genes, 217–218

Genotoxin, 555Gentamicin, 194, 423, 570–572, 573, 592Gentamicin as say, 199, 201Gentamicin pro tec tion as say, 193, 194, 200

cell ad he sion and in va sion, 193–195Germ-free (GF), 148Germfree an i mals, 100, 187, 228, 264Germ the ory of in fec tious dis ease, 136Giardia, 7Giardia intestinalis, met ro ni da zole, 426Gillray, James, 477Gingivitis, 147Glassification, 504Global Alliance for Vaccines and Immunization (GAVI), 480Global reg u la tor, 362Global vir u lence reg u la tion, 467Glycopeptides, 420–421, 452Glycoproteins, 64Glycosaminoglycans, 25Glycosyltransferases, 161Gnotobiotic an i mals, 187, 228Gnotobiotic pig lets, 264Goblet cells, 32, 263Gram-negative bac te ria

ad her ence mech a nisms, 269model for pili as sem bly, 272pili (fim briae) of, 270–271, 273quo rum-sensing of, 380re view of, 15–16

Gram-negative op por tu nis tic path o gen(s)Acinetobacter baumannii, 565–567Bacteroides fragilis, 555–557Burkholderia cepacia com plex, 565com mon traits of, 549–550Ehrlichia spp., 567ev er-changing face of Escherichia coli, 550–554Klebsiella pneumoniae nos o co mial in fec tions, 554–555Porphyromonas gingivalis, 557–558, 559Pseudomonas aeruginosa, 558, 560–565


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

670 • INDEX

Gram-positive bac te riamodel of pi lus as sem bly, 274pili (fim briae) of, 273–274quo rum-sensing of, 380re view of, 15–16spe cial ized se cre tion sys tems, 340, 350–353

Gram-positive bac te rial sortases, 521Gram-positive op por tu nis tic path o gen(s), 515–516, 542–543

char ac ter is tics of, 516Clostridium dif cile, 534–542Staphylococcus au re us, 516–524Staphylococcus epidermidis, 524–527Streptococcus pneumoniae, 527–534

Granulocyte-macrophage col ony stim u lat ing fac tor (GM-CSF), 63Granulocytes, 41, 44, 47Granulysin, 81Granzymes, 49, 81Grays, 403Green fluo res cent pro tein (GFP), 231Griffi th, Fred er ick, 163, 166, 527Gut microbiome, Salmonella enterica serovar Typhimurium

in fec tion, 247

Haemophilus, microbiomes of new born in fants, 123Haemophilus influenzae, 37, 163, 186, 277, 483

men in gi tis, 278–279re spi ra tory tract, 37

Haemophilus influenzae type B (HIB)mor bid ity be fore and af ter vac cines, 488rec om mended im mu ni za tion sched ule, 491

Haemophilus influenzae type b (Hib) vac cine, 479side ef ect re view, 486–487

Haemophilus parainfluenzae, 163Hamamelitannin, 430Hamiltonella defensa, 356–357, 392–393Handwashing, 30–31Hazard anal y sis and crit i cal con trol point (HACCP),

11–12, 587Heart dis ease, 12Heat-labile toxin (HLT), 302, 551Heat shock pro teins, 497Heat-stable toxin (HST), 302, 551Heat treat ment, 402–403Heidelberger, Mi chael, 527Helicobacter, 35, 186Helicobacter mustelae, 142, 262Helicobacter py lo ri, 6, 34, 132, 154, 163, 165, 245, 261,

268, 302, 592col o ni za tion, 290elim i na tion for dis ease cure, 144, 146–147evad ing com ple ment, 278gas tric ul cers, 139ge no mic plas tic ity, 377iso lat ing, 140knock out and knock-in mice, 187met ro ni da zole, 426No bel Prize, 142, 154old dogma vs. new model, 145pen e trat ing mu cin layer, 263–264pro posed mech a nism for gas tric ul cer for ma tion, 280re search, 142rev o lu tion, 12–13, 14

Hemagglutination, 271Hemagglutinins, 180

Heme, 266Hemoglobin, 266Hemolysin (Hly), 302α-Hemolysin, 307Hemolysin fam ily, 308Hemolysis, 306Hemolytic ure mic syn drome (HUS), 550, 551Hemorrhaging, 67Henle, Frie drich Gus tav Ja cob, 136Heparin, 47Heparin-binding epi der mal growth fac tor-like growth fac tor

(HB-EGF) pre cur sor, 317Hepatitis A, rec om mended im mu ni za tion sched ule, 491Hepatitis B, rec om mended im mu ni za tion sched ules, 491Hepatitis B vi rus, 12Hepatitis C vi rus (HCV), 492Hepatitus B vac cine (HBV), side ef ect re view, 486–487Hepatotoxin, 301Herd im mu nity, 485, 488, 528Hexachlorophene, 406Hfq, 372Hib (Haemophilus influenzae type b), 490High-frequency re com bi na tion (Hfr), 167High mo bil ity group box 1 (HMGB1) pro tein, 54High-performance liq uid chro ma tog ra phy (HPLC), 120, 246High-throughput screen ing (HTS), 411Hin (DNA in ver tase), 159, 161Hirudo medicinalis, 187Histamine, 47, 78Histatins, 34Histidine ki nase, 364HIV, 128, 184, 187, 492, 493HNH, 238H-NS (his tone-like nu cle oid struc tur ing), 375–376Holin, 171, 537Homology-directed re pair (HDR), 237Horizontal gene trans fer (HGT), 4, 158, 347, 438

con ju ga tion of plas mids and trans po sons, 165–167, 169con trol of, 171, 173–174CRISPR-Cas sys tems, 173–174nat u ral trans for ma tion, 162–165phage trans duc tion, 171, 172of re sis tance genes, 461–463re sis tance in na ture, 464re stric tion-modification sys tems, 173tox in-antitoxin sys tems, 171, 173type 6 se cre tion sys tems, 174

Hospital-acquired (nos o co mial) in fec tions, 6Hospital-associated meth i cil lin-resistant S. au re us (HA-MRSA),

470, 509, 544–545Hospitals, mak ing safe for pa tients, 12Host

mim ick ing the, 277–278see al so Immune re sponses

Host cells, in va sion and up take by, 280–281Host de fenses, breaches of, in U.S. his tory, 29Host fi bro blast ex per i ment, 571Host-microbe re la tion ship, 5Host-pathogen in ter ac tion, mod el ing in ex per i men tal an i mals,

17–18House Energy and Commerce Committee, Subcommittee on

Health, 439Human im mu no de fi ciency vi rus (HIV), 8Humanized trans genic an i mal mod els, 230


IP: 54.70.40.11

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INDEX • 671

Human-microbe in ter ac tionsva ri e ties of, 150views of, 150, 152

Human Microbiome Project (HMP), 115Human microbiota

new born in fants, 123oro pha ryn geal, 125over view of, 123–128skin, 124small in tes tine and co lon, 125–126, 128vag i nal tract, 128, 129see al so Microbiota

Human monocytotrophic ehr lich i o sis (HME), 567Human pap il loma vi rus (HPV), 12, 147, 491, 492Human re spi ra tory syn cy tial vi rus (HRSV), 493Humoral im mu nity, 74Hyaluronate ly ase, 529Hyaluronic acid, 277, 288Hyaluronidases, 288Hydrogen per ox ide, 407Hydrophobicity plot, 332Hydroxamates, 266α-Hydroxyketones (AHK), 379, 380, 381Hypermucoviscous phe no type, Klebsiella pneumoniae, 554, 555Hypermutable, 377Hypersensitivity, 80Hypochlorite, 56Hypotension, 66, 68Hypothiocyanite, 56

iC3b, 63ID50 (50% in fec tious dose), 190IFN-γ, 63IgD, 78

struc ture of, 75IgE, 78

struc ture of, 75IgG, 74, 76–77

struc ture of, 75IgM, 77–78

struc ture of, 75IL-1 re cep tor an tag o nist, 65Illumina RNA-Seq tech nol ogy, 240Illumina se quenc ing tech nol ogy, 109, 110Immune de fenses, skin and mu cosa, 37–38Immune po ten ti a tors, 494Immune re sponses

cy to kines and che mo kines as me di a tors of, 63–65evad ing the host, 275, 277–289

Immune sys tem(s)an ti gen pre sen ta tion, 82–88links be tween in nate and adap tive de fense, 88

Immunization, pas sive, 504Immunization pro grams, 480–485

antivaccination move ment, 484–485bar ri ers to im ple men ta tion and suc cess, 483–484de vel op ment stages, 482in fra struc ture fail ing to main tain, 481

Immunization sched uleper sons age 0–6 years, 491per sons age 7–18 years, 491

Immunoblotting, 345Immunofluorescence mi cros copy, 143, 144Immunogen, 76, 479

Immunogenic, 76Immunoglobulin (Ig), 74

bind ing by pro tein A, 522Immunohistochemistry, 143, 144Immunomodulation, 296Immunoprecipitation (IP), 523Immunoproteomics, 246Immunotoxins, 329Inactivated po lio vi rus, rec om mended im mu ni za tion sched ule, 491Indels, 158Indication, 415Indirect as so ci a tion, 234Indirect ELISA, 143, 145Indolyl-galactoside (X-gal), 208Induced tol er ance, 494Infant bot u lism, 320Infant mice, 228Infection

an i mal mod els of, 184–188com par a tive ap proaches to iden ti fy ing host fac tors for, 227–235host re sponse pro fil ing to iden tify host fac tors for, 240–247in vi vo im ag ing of an i mals dur ing, 231screen ing ap proaches to iden ti fy ing host fac tors for, 235–240

Infectious dis eas esbioterrorism, 8, 10de fense against, 23–24emerg ing and re emerg ing, 6–7foodborne and wa ter borne, 7–8mod ern med i cine as source of new, 8–9post sur gi cal, 9–10re spect for pre ven tion, 10–11wound, 9–10

Inflammasome, 51Inflammation, col lat eral dam age and, 65Inflammatory bowel dis ease (IBD), 39, 128, 135Inflammatory re sponse, 47Influenza, rec om mended im mu ni za tion sched ule, 491Influenza vi rus, 37Injection-free vac cines, 502Injectisome, 343Innate im mune re sponses, roles of cy to kines and che mo kines, 63–65Innate im mune sys tem, 41

cells de fend ing blood and tis sue, 42, 47–50com po nents and ac tiv i ties of, 43–44nu tri tional im mu nity, 69sep tic shock, 66–69Toll-like re cep tor fam ily and sig nal ing path ways, 52trig ger ing de fenses, 41–42

Innate im mu ni tyevad ing host’s, 264–265evad ing im mune rec og ni tion and opsonization, 264or gan isms, 93re sis tance to an ti bac te rial pep tides, 264–265

Insertion se quence (IS), 169, 457Insertion se quence (IS) el e ments, 461–462Institute of Medicine (IOM), 486–487Institutional Animal Care and Use Committee (IACUC), 188Institutional re view boards (IRBs), 414Integrative conjugative el e ment (ICE), 167Integrins, 25, 26, 63, 497Integron, 462Intellectual prop erty (IP), 413Intercellular ad he sion mol e cules (ICAMs), 63Intergenic, 464


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

672 • INDEX

Intergenic re com bi na tion, 162Interleukin-1 (IL-1), 65Interleukin-3 (IL-3), 63Interleukin-4 (IL-4), 65Interleukin-6 (IL-6), 65Interleukin-8 (IL-8), 63Interleukin-10 (IL-10), 65Interleukin-13 (IL-13), 65Internal hem or rhages, 68Internalins, Listeria monocytogenes, 275, 276Internal tran scribe spacer (ITS), 130International Nucleotide Sequence Database (INSD), 103Intestinal ep i the lial lym pho cytes (IELs), 91Intracellular path o gens

autophagy for kill ing, 56NOD-like re cep tor (NLR) sens ing of, 54

Intragenic, 464Intragenic re com bi na tion, 162Intranasal in oc u la tion, 502Invasins, 281Invasion fre quency, 195Invasion-induced sig nal ing, or gan isms, 93Invasion suc cess curve, 195Inversion of se quences, 159Investigational new drug (IND), 413In vi vo-induced an ti gen tech nol ogy (IVIAT), 218–219, 221, 246In vivo in fec tion mod els, 231Ionizing ir ra di a tion, 403Ion Torrent tech nol ogy, 110Iraq War, 10

Acinetobacter baumannii, 565–567Iron ac qui si tion

bac te ria, 266, 268bac te rial siderophores, 268mech a nisms, 267

Irradiation of food, 587–589Irradiation tech nol ogy, his tory of food, us age, 403Ischemia, 66Isoelectric fo cus ing (IF), 243Isoelectric point (pI), 243Isolation mem brane, 56Isoniazid

fail ure to ac ti vate, 453–454KatG cat a lyzed ac ti va tion of, 454

Janthinobacterium lividum, phy lo ge netic trees, 105J-chain, 77Jen ner, Ed ward, 477Jew ish Chronic Disease Hospital, 184JGI Genomes (Department of Energy Joint Genome Institute), 103

Kallidin, 65Kanamycin, 423KEGG Orthology (Kyoto Encyclopedia of Genes and Genomes), 103Ken nedy, John F., 29Keratinocytes, 32Ketolides, 429Keystone path o gen, 148, 149, 557Kirby-Bauer disc dif u sion as say, 404, 405Klebsiella spp., 35, 36Klebsiella pneumoniae, 6, 31, 201, 549

dis eases and breach in de fenses, 550ESKAPE, 440hypervirulence, 554–555

mul ti drug re sis tance, 555nos o co mial in fec tions, 554–555pili, 271

Knock-in mice, 187Knockout mice, 187Koch, Rob ert, 137, 204Koch’s pos tu lates

as so ci a tion of mi crobe with le sions of dis ease, 139–140chal lenges to sat is fy ing, 138–143his tory and rel e vance of, 136–138iso lat ing bac te rium in pure cul ture, 140–141mi crobe-disease con nec tion, 137–138mod ern al ter na tives to sat isfy, 143–147mo lec u lar, 149–150reisolating bac te rium in in ten tion ally in fected an i mal, 143show ing iso lated bac te rium caus ing dis ease, 141–143then and now, 137

β-Lactam an ti bi ot ics, 417–420mech a nism of ac tion, 419struc ture of, 419

β-Lactamases, 446ac tion of, 447en zy matic in ac ti va tion of, 446–448ex tend ed-spectrum (ESBLs), 448reg u la tion of re sis tance genes, 455zinc-, 448

β-Lactams, re sis tance to, 451–452Lactobacillus sp., 35, 36, 100, 104, 106, 107

co lon microbiota, 126microbiomes of new born in fants, 123vag i nal microbiota, 112, 128

Lactobacillus crispatus, 105, 112, 114Lactobacillus fornicalis, 105Lactobacillus gasseri, 105, 112, 114Lactobacillus iners, 105Lactobacillus jensenii, 112Lactoferrin, 33, 43, 266Lactoperoxidase, 33Laminins, 25Lang er hans, char ac ter is tics of, 43Lang er hans cells, 37, 47, 90Laser-capture mi cro dis sec tion (LCM), 243, 244Lateral sur faces, 192Lawsonia ferretii, 250LC3, 56LD50 (50% le thal dose), 190Leader pep tide, 454Leader re gion, 454Leader se quence, 336Lectin path way, 58, 59, 61Leeches, 187Legionella, 7, 195

fac ul ta tive path o gen, 282, 283, 284flu o ro quin o lones, 427

Legionella pneumophila, 163, 234–235, 258, 260Legionnaires’ dis ease, 154, 258, 260Leprosy, 87Leptospira spe cies, 304Leptotrichia amnionii, 105Lethal fac tor (LF), 310Leukocidin, pore for ma tion by, 520Leukocytes, 41, 44Leukotoxin, 301


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

INDEX • 673

Libraries, 410Lin coln, Abra ham, 29Lincomycin, 425Lincosamides, 425, 452Linezolid, 429, 438Linkage, 234Lipase tox ins, 299Lipid A, 302Lipinski’s Rule of Five, 412Lipooligosaccharide (LOS), 161, 265Lipopeptides, 420Lipopolysaccharide (LPS), 14, 51, 265, 302

bac te rial mem brane, 300cel lu lar rec og ni tion of, through Toll-like re cep tor sig nal ing, 53proinflammatory cy to kine re lease by Gram-negative, 67

Liposomes, 496, 498Lipoteichoic acid (LTA), 14, 51, 302Lis ter, Jo seph, 136Listeria, 195, 373Listeria monocytogenes, 114, 224, 250, 591

ac tin-based mo til ity, 282, 286–287adhesins, 275an ti bi otic re sis tance, 470–472es cap ing phagosome, 281gene si lenc ing, 235, 236hu man ized trans genic mice, 230internalins and host cell re cep tors, 275, 276in tra cel lu lar life cy cle of, 281, 282or ga ni za tion and con trol of vir u lence genes, 362reg u la tory net work, 370screen ing, 208trans po son, 290

Locus of enterocyte ef ace ment (LEE), 551Lon don ep i demic chol era, 146Loose con nec tive tis sue, 25, 26LPS-binding pro tein (LBP), 51Luciferase-catalyzed bio lu mi nes cence, 383Lyme dis ease, 95, 304, 510Lymph, 50Lymphadenopathy, 50Lymphatic sys tem, 50Lymph nodes, 50Lymphocytes, 44Lyophilization, 504Lysis, 376Lysogenic corynebacteriophages (β-phage and ω-phage), 315, 317Lysogenic phages, 171Lysogenic phase, 171Lysogeny, 376Lysosomes, 55, 57Lysozyme, 27

ac tion of, 33char ac ter is tics and func tions of, 44

LytA (N-acetylmuramoyl-L-alanine am i dase), 531Lytic phase, 171

M (microfold) cells, 90McCarty, Maclyn, 163, 527McComb, Bach, 322Mc Kin ley, Wil liam Jr., 29Mac leod, Colin, 163, 527Macrolactones, 300Macrolides, 424–425, 451, 452Macromolecular an ti gens, 84

Macrophage cy to plasm, 287Macrophages, 42, 43Magnetotaxis, 262Major his to com pat i bil ity com plex (MHC), 82Major his to com pat i bil ity com plex, class 1 (MHC I), 49–50, 82,

83, 84Major his to com pat i bil ity com plex, class II (MHC II), 82, 83, 84Male uro gen i tal tracts, 36Managed health care or ga ni za tions, 12Manhattan plot, 234Mannose-binding lec tins (MBL), 58, 59Mar cus, Steven, 322Margination, 64Marshall, Barry, 142, 145, 154Mass spec trom e try (MS), 120Mast cells, 42, 47, 78Matrix, 192MBL-associated ser ine pro te ase (MASP) pro teins, 61M cells, 263M cells (microfold cells), 38MD2, 51Measles, mor bid ity be fore and af ter vac cines, 488Measles, mumps, ru bella (MMR), rec om mended im mu ni za tion

sched ule, 491Measles vac cine

side ef ect re view, 486–487time lines and im pact, 478

Mechanism-based in hib i tor, 422Mechanisms of ac tion

an ti bi ot ics and, 408an ti bi ot ics tar get ing DNA and RNA syn the sis, 425–429cell wall syn the sis in hib i tors, 417–422in hib i tors of tetrahydrofolate bio syn the sis, 429newest an ti bi ot ics, 429–430newest an ti bi otic tar gets, 430pro tein syn the sis in hib i tors, 422–425strat e gies for en hanc ing an ti bi otic effi cacy, 431–432tar gets of an ti bi otic ac tion, 416–417

Mechanisms of an ti mi cro bial re sis tance, 402Membrane at tack com plex (MAC), 58, 60Membrane-disrupting tox ins (Type II tox ins), 306–307Membrane-hydrolyzing tox ins, 309Membrane im mu no glob u lin (mIg), 522Membrane im mu no glob u lins, 82Memory T cells, 85Meningitis, 553Meningococcal, rec om mended im mu ni za tion sched ule, 491Mersacidin, 418Metabologenomics dis cov ery ap proach, 414Metabolomes, 246Metabolomics, 101, 120, 122, 222, 246–247Metagenome, 115

be yond the, 117–122pro te o mics and metabolomics, 120–122RNA-seq pro fil ing (transcriptomics), 118–120

Metagenomic anal y sis, 115, 117Metatranscriptomics, 118Methanobrevibacter, 35Methicillin, evo lu tion of re sis tance, 438Methicillin-resistant Staphylococcus au re us (MRSA), 6, 10, 31, 417,

439, 463, 509, 516, 544–545com mu ni ty-acquired (CA-MRSA), 355, 470, 509, 544–545hos pi tal-acquired (HA-MRSA), 470, 509, 544–545spread of, 470


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

674 • INDEX

Metronidazole, 425, 425–426, 435ac ti va tion of, 426fail ure to ac ti vate, 453in hib it ing DNA and RNA syn the sis, 426struc ture of, 426

MF59, 495MHC 1-specific in hib i tory re cep tor, 50Miasma the ory, 136MICA, 92MICB, 92Microarrays, 240Microarray tech nol ogy, 240Microbial cen sus

com par a tive 16S rRNA gene-based pro fil ing of com plex mi cro bial com mu ni ties, 112

mi cro bial rRNA gene se quence anal y sis, 101, 104, 106–115PacBio SMRT se quenc ing plat form, 109, 111quan ti ta tive re al-time PCR (qPCR), 107–109track ing mi crobes through space and time, 112, 114–115ul tra-high-throughput, mas sively par al lel DNA se quenc ing,

109–110Microbial com mu ni ties, 147

16S rRNA gene-based pro fil ing of com plex, 112com par a tive 16S rRNA gene-based pro fil ing of com plex, 112Koch’s pos tu lates and path o genic, 147metagenomic pro fil ing of strain-level var i a tion, 117phylochips for pro fil ing, 113phy lo ge netic trees show ing re la tion ship, 105prin ci pal com po nent anal y sis for re la tion ships, 106

Microbial dysbiosis, 147Microbial evo lu tion, over view of, 4Microbial ge nomes

min ing, for new an ti bi ot ics, 413Microbial pop u la tion shift, 147Microbicidal, 404Microbiomes, 5, 101, 115, 117Microbiostatic, 404Microbiota, 13, 99–100, 147

char ac ter iza tion of body’s, 100–129for got ten eu kary otes, 130nor mal, of skin and mu cosa, 27–29, 31obe sity, 127oro pha ryn geal, 125over view of hu man, 123–128sche matic of ac tiv i ties of co lonic, 126skin, 124small in tes tine and co lon, 125–126, 128vag i nal tract, 128, 129

Microbiota-gut-brain axis, 125Microbiota shift dis eases, 6, 13–14

key stone path o gens and dis ease, 147–149Microcapsules, 496Microcin E492, 555Micrococcineae, microbiomes of new born in fants, 123Microspheres, 496Minimal bac te ri cidal con cen tra tion (MBC), 404Minimal in hib i tory con cen tra tion (MIC), 404Min-ION plat form, nanopore se quenc ing tech nol ogy, 214Mitochondria, 5MMR vac cine, 482mob genes, 461Mobile ge netic el e ment (MGE), 166Mobilizable, 169Mobilizable plas mids, 461

Model(s)as sem bly of pili in Gram-negative bac te ria, 272cor re la tion stud ies, 18curli pi lus reg u la tion and as sem bly, 273or gan cul ture, 196–197pi lus as sem bly in Gram-positive bac te ria, 274tis sue cul ture, 192–193vir u lence gene ex pres sion and bac te rial growth, 257see al so Animal mod els

Molecular ge netic ap proachesmu ta gen e sis screen ing, 210–214re porter fu sions, 208–210screen ing us ing re com bi nant genes, 208

Monobactams, 417, 419Monocytes, 42, 43Monophosphoryl lipid A (MPL), 497Moraxella bovis, pili, 271Moraxella catarrhalis, 37M pro tein, 275MSCRAMMs (mi cro bial sur face com po nents rec og niz ing ad he sive

ma trix mol e cules), 520Mucin, 32, 263Mucinase, 263Mucosa. See Skin and mu co saMucosa-associated lym phoid tis sue (MALT), 27, 38, 90, 91, 187Mucosal ep i the lia, 24Mucosal im mu ni ty

ed i ble vac cines, 502–503ex per i ment dem on strat ing, at re mote sites, 91IgA/sIgA an ti bod ies, 89–92Injection-free vac cines, 502tox ins to stim u late, 502vac cine vec tor tech nol ogy, 500–502

Mucosal mem brane, 193Mucosal sur faces, de fenses of, 27, 32–34Mucus, 27, 263Multidrug ef ux pumps, 441Multidrug ef ux sys tem, 341Multidrug re sis tance (MDR), 440–441, 555Multifunctional au to-processing re peats-in-toxin (MARTX)

toxin, 302Multilocus se quence anal y sis (MLSA), 115Multilocus se quence typ ing (MLST), 112, 114–115Multilocus trait anal y sis (MLTA), 235Multiorgan microphysiological sys tems, 197, 198Multiplexed, 143Multiplexing, 107Multiplicity of in fec tion (MOI), 193Multisubunit AB-type tox ins, 298Mumps

mor bid ity be fore and af ter vac cines, 488side ef ect re view of vac cine, 486–487

Mupirocin, 417Mus musculus, 233Mutagenesis screen ing, 210–214Mutagenesis stud ies, 357–358Mycobacteria, 15Mycobacterium spp.

diarylquinoline com pounds, 429–430zebrafish model, 186

Mycobacterium bovis, 223, 229Mycobacterium leprae, 32, 87Mycobacterium tu ber cu lo sis, 87, 185, 515

ac id-fast stain ing, 139


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INDEX • 675

fac ul ta tive path o gen, 282, 283, 284iso lat ing, 140, 141reg u la tory net work, 370re sis tance to an ti bi ot ics, 442, 442–444(g00d)sigma fac tors and func tions in, 368

Mycobacterium ulcerans, 206, 305Mycolactones, 305Mycolactone tox ins, 304Mycoplasma spp.

flu o ro quin o lones, 427phase var i a tion, 160

Mycoplasma genitalium, 222Mycoplasma penetrans, 162Mycoplasma pneumoniae, 37Myeloperoxidase, 55

NADPH ox i dase, 55Nalidixic acid, 427Nanopore se quenc ing tech nol ogy, 214Nasopharyngeal-associated lym phoid tis sue (NALT), 38, 90National Academy of Sciences, 485National Institutes of Health (NIH), 11, 184, 581, 582, 589National Science Advisory Board for Biosecurity, 585National Wildlife Health, 224Native PAGE, 243Natural killer (NK) cells, 41, 43, 48–50Naturally com pe tent, 163Naturally trans form able, 163Natural prod ucts, 409–410Natural trans for ma tion, 163, 167NCBI (National Center for Biotechnology Information), 103NDP52, 56Necrotizing fas ci i tis, 288Neelsen, Frie drich, 139Neisseria spp.,179, 180, 493

microbiomes of new born in fants, 123outer mem brane pro teins, 163phase var i a tion, 160–161pili, 271

Neisseria equiniae, 200Neisseria gonorrhoeae, 128, 161, 162, 163, 392, 508Neisseria meningitidis, 161, 163, 187, 200, 508

an ti genic var i a tion, 164bac te rial men in gi tis, 278–279re spi ra tory tract, 37

Neisseria meningitidis se ro type B, 492Neonatal men in gi tis-causing E. coli (NMEC), 553–554Neuraminidase NanA, 529Neurotoxin, 301Neutralization of path o gen, 79Neutropenic mice, 228, 229Neutrophil(s), 42, 48Neutrophil ex tra cel lu lar traps (NETs), 42, 560Neutrophilia, 66New En gland Journal of Medicine (jour nal), 14New York Chamber of Commerce, 438Ni colle, Charles, 231Nitric ox ide, 56Nitrofurantoin, 425–426

ac ti va tion of, 426struc ture of, 426

NMPDR (National Microbial Program Data Resource), 103No bel Prize, 142, 154, 204NOD1 pro teins, 52

NOD2 pro teins, 52Node, 104NOD-like re cep tors (NLRs), 51

in tra cel lu lar path o gens sens ing, 54Nodosome, 53NOG and NSG (NOD SCID) mice, 228Nonhomologous end join ing (NHEJ), 237Nonmammals, adap tive de fense sys tems in, 93Nonoxidative kill ing, 55Nonprotein tox ins, 302–304Norfloxacin, 427Nosocomial, 440Nosocomial in fec tions, 6, 9NRAMP1, 69Nramp1 (nat u ral re sis tance–as so ci ated mac ro phage pro tein-1), 228Nuclear lo cal i za tion sig nal (NLS), 345Nuclear mag netic res o nance (NMR) spec tros copy, 120Nucleoid, 375Nucleoid-associated pro teins (NAPs), 375Nude mice, 228Nutrient ac qui si tion, bac te ria, 265–266Nutritional im mu nity, 69

O an ti gen, 302Obesity, 127Oblate in tra cel lu lar path o gens, 282, 283Occult bac ter emia, 531Oligopeptide autoinducers, 379Open read ing frames (orfs), 16, 235, 270Operational tax o nomic unit (OTU), 104Operators, 363Operon, 362Operon fu sions, 208Opportunistic path o gen(s), 4, 8–9, 288–289

breaches in hu man de fenses by, 550char ac ter is tics of Gram-positive, 516de scrip tion of, 515–516term, 515see al so Gram-negative op por tu nis tic path o gen(s); Gram-positive

op por tu nis tic path o gen(s)Opsonin, 59Opsonization, 58, 59, 264

by C3b, 60by IgG, 60

Optineurin (OPTN), 56OPV/IPV, side ef ect re view, 486–487Oral bac te ria, cor o nary ar tery dis ease and, 558Oral re hy dra tion ther apy (ORT), 327, 328Organ cul ture mod els, 196–197Oronasopharyngeal, 24Oropharyngeal microbiota, 125Os ler, Sir Wil liam, 527Outer mem brane pro tein A (OmpA), 554Oxazolidinones, 429Oxidative burst, 55, 281

bac te rial eva sion sys tem, 286in phagolysosomes, 54–56

Oxidative kill ing, 55

p62, 56Pacific BioSciences (PacBio), sin gle-molecule, re al-time (SMRT)

se quenc ing, 109, 111Paired-end se quenc ing, 109, 110PaLoc (path o ge nic ity lo cus), 537


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

676 • INDEX

Pandemic, 483Pan-drug re sis tant (PDR), 441Paneth cells, 32, 35Pan-genome, 178Panresistant, 567Panton-Valentine leu co ci din (PVL), 520Paralogs, 51Paramecium, sur vival, 258Park, Wil liam H., 204Passive im mu ni za tion, 315, 504, 506Pas teur, Louis, 136Pasteurella, 291, 292Pasteurellaceae, 123, 291–292Pasteurella multocida, pili, 271Pasteurella multocida toxin (PMT), 302Pasteurization, 136, 402Patch, 502Pathoadaptation model, bac te ria path o gen evo lu tion, 177Pathogen-associated mo lec u lar pat terns (PAMPs), 42

de tec tion of ex tra cel lu lar, 54de tec tion of in tra cel lu lar, 54

Pathogenesisevo lu tion, 6, 17, 177–178global per spec tive, 291–292re search, 14, 16–18, 197–198

Pathogenesis re search, 14, 16–18, 197–198Pathogenic bac te rium Q (QPS), 95Pathogenicity is lands (PAIs), 174, 176–177, 343Pathogens

iron ac qui si tion, 266, 267, 268nu tri ent ac qui si tion, 265–266vir u lence fac tors, 255–257

Pattern rec og ni tion re cep torsor gan isms, 93in pneu mo coc cal in fec tion, 532

PCV-7 (pneumonococcal con ju gated 7–valent vac cine), 528Pedestal for ma tion, 551Pel o pon ne sian War, 477Penicillin(s) 417, 418, 419, 438Penicillin-binding pro teins, 418, 451Peptide an ti gens, 82, 84Peptides, 298Peptidoglycan (PG) 51, 302

mono mer, 303steps in bio syn the sis of, 418

Peptococcus, 35Peptostreptococcus, 35Perforin, 48, 81Periodontal dis ease, 13, 147, 153–154, 557–558Periodontitis, 148Periodontium, 147Peroxiredoxins (Prx), 285, 288Peroxynitrite (OONO-), 56Persistence, an ti bi otic re sis tance, 459Persister cells, 459Pertactin (Pn), 488Pertussis (whoop ing cough), 304, 483, 488Pertussis toxin (PT), 307, 310Pertussis vac cine, 485, 488, 489, 490Petechiae, 67Petri, Julius Rich ard, 138Peyer’s patches, 90, 92, 100Pfam (Protein Families and Domains), 103Phage dis play, 218

Phage trans duc tion, 171, 172Phagocyte(s), 41, 44

kill ing bac te ria, 54–56rec og ni tion and re sponse to bac te ria, 50–54steps in in ges tion and kill ing of bac te ria, 55trans mi gra tion, 47–48

Phagocytic cells, 5, 41Phagocytose, 42Phagocytosis, 5, 54

avoid ing com ple ment and, 277–278, 280neu tral i za tion or re sis tance to phagolysosomal com po nents, 285re sis tance to re ac tive ox y gen and ni tro gen spe cies, 285–286sur viv ing, 281–286

Phagolysosomes, ox i da tive burst in, 54–56Phagophore, 56Phagosome, 54, 281, 287

es cape from the, 281–282pre ven tion of phagolysosomal fu sion, 282–283, 285

Phalloidin, 196Pharmacokinetics, 405, 407Phase var i a tion

bistable switches and, 376–377Bordetella by slipped-strand re pair, 163ge netic change, 159–161Mycoplasma penetrans, 162

Phenol-soluble modulins (PSMs), 525Phosphatidylethanolamine (PE), 56Phospholipase, 33, 307Phospholipid, 309Phosphorelay, 367Phosphorylcholine (P-Cho), 529Photinus pyralis, 231Phototaxis, 262Phylochips, 112, 113Phylogenetic re la tion ships, microbiome pro files of hu man body, 124Phylogenetic tree(s), 104

ra dial, 107re la tion ships among mi cro bial com mu ni ties, 105

Phylotypes, 112Pilicides, 271, 467Pili/fimbriae, 268

im mune re sponse, 277model for as sem bly, 272reg u la tion and as sem bly, 273

Pilin, 270Pilus, 268Plaque, 195, 260Plaque as say, 195–196Plasma cells, 74Plasmids, 165

con ju ga tion with trans po sons, 165–167, 169self-transmissible and mobilizable conjugative, 168

Plasmin, 519Plasminogen, 519Platelet-activating fac tor (PAF), 64Platelet-activating fac tor re cep tors (PAFR), 529Platelet-endothelial cell ad he sion mol e cule (PECAM), 64Plesiomonas shigelloides, mo til ity, 262Pneumocins, 527Pneumococcal, rec om mended im mu ni za tion sched ule, 491Pneumococcal ad her ence and vir u lence fac tor A (PavA), 529Pneumococcal sur face adhesin (PsaA), 529Pneumolysin, 529Pneumonia, Burkholderia cenocepacia, 565


IP: 54.70.40.11

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INDEX • 677

Polarized, 192Polarized cells, 25Poliomyelitis, mor bid ity be fore and af ter vac cines, 488Polio vac cine, time lines and im pact, 478Poly(I:C), 497Poly-γ-glutamic acid (PGA), 525Poly-Ig re cep tor, 90, 530Polyketide synthases, 304Polymerase chain re ac tion (PCR), 101

16S rRNA gene am pli fi ca tion, 102quan ti ta tive re al-time PCR (qPCR), 107–109

Polymorphonuclear leu ko cytes (PMNs), 42, 43Polytopic, 336Polyvalent an ti gen, 78Pore-forming tox ins, 298, 307, 308Porphyromonas gingivalis, 133, 180, 291, 511, 549

dis eases and breach in de fenses, 550key stone path o gen, 149model of in va sion and per sis tence, 559oral bac te ria and cor o nary ar tery dis ease, 558oro pha ryn geal microbiota, 125peri odon tal dis ease, 148, 153–154, 557–558

Positive feed back loop, 369Postal work ers, 581Postsurgical in fec tions, 9Posttranscriptional gene si lenc ing, 236Prebiotics, 100Precision med i cine, 100Preinfection

bio films, 258–260mo bil ity and che mo taxis, 260–263sur vival in ex ter nal en vi ron ment, 258

Preservation of Antibiotics for Medical Treatment Act (PAMTA), 439Preterm birth, 560Prevention, in fec tious dis eases, 10–11Prevotella sp., 35, 107, 148

microbiomes of new born in fants, 123oro pha ryn geal microbiota, 125

Prevotella bivia, 105Principal com po nent anal y sis (PCA), 104, 106Pristinamycin, 432Probiotics, 100, 466Progenitor toxin, 321Programmed cell death, 49, 81Promoter mu ta tions, 457Properdin (P), 62Prophages, 171Propionibacterineae, microbiomes of new born in fants, 123Propionibacterium ac nes, 28, 29Prospective study, 184Pro tag o ras of Abdera, 99Protein A, 522, 523Protein-conducting chan nel, 336Protein da ta bases, 16Protein G, 523Protein mi cro ar ray, iden ti fy ing in vi vo-expressed pro teins, 219Protein mi cro ar rays, 218, 245Protein syn the sis in hib i tors, 422–425

aminoglycosides, 423lincosamides, 425macrolides, 424–425tet ra cy clines, 423–424

Proteoarrays, 218, 220Proteobacteria, 35, 104

Proteomic pro fil ing, 243Proteomics, 101, 120, 121, 122, 222, 243, 245–246Pro teus, 35Pro teus mi ra bi lis, 36, 262Proton mo tive force (PMF), 260, 266Protospacer-adjacent mo tif (PAM), 238Protozoa, 5Pseudogenes, 280Pseudomembrane, 315, 537Pseudomembranous co li tis, 535, 538Pseudomonas spp., 106, 259Pseudomonas aeruginosa, 10, 31, 37, 206, 231, 240, 260,

261, 374, 549ad her ence mech a nism, 269cap sule com po si tion, 278dis eases and breach in de fenses, 550ESKAPE, 440, 562lung in fec tions in cys tic fi bro sis pa tients, 560–561model of, dis sem i nat ing from lung into blood stream, 564model of co op er a tion be tween type IV pili and exolysin A, 564neu tro phils and, in cys tic fi bro sis lung in fec tions, 561outer mem brane porins, 445phen a zine-derived tox ins by, 207pili, 271re sis tance to an ti bi ot ics, 562, 564–565vir u lence fac tors, 561–562, 563–564wound and burn in fec tions, 558, 560

Pseudomonas brenneri, 105Pseudomonas fluorescens, 379Pseudomonas fragi, 105Pseudomonas gessardii, 105Pseudomonas poae, 105Pseudomonas syringae, 370Pseudomonas taetroleus, 379Psoralen, 501Public health, bac te ria and, 3–4Public Health Department, 8PubMed, 103Puerperal fe ver, 30Pulldown as say, 523Purulent, 65Pus, 65, 288Pyocyanin, 561Pyogenic, 65Pyroptosis, 52Pyruvate ox i dase (SpxB), 531

QPS (path o genic bac te rium Q), 95QS-21, 495, 496, 497Quantitative re al-time po ly mer ase chain re ac tion (qPCR),

107–109, 241Quantitative trait, 234Quantitative trait loci (QTL), 231Quaternary am mo nium com pounds (QACs), 407QuilA, 495Quinolones, 427–429

re sis tance to, 452–453Quinupristin, 432Quorum, 378Quorum sens ing, 378–387, 389

Agr sys tem of Staphylococcus au re us, 385, 387autoinducers, 379block ing, 467Gram-negative and Gram-positive bac te ria, 380


IP: 54.70.40.11

On: Sat, 03 Aug 2019 02:34:05

678 • INDEX

Quorum sens ing (continued )Lux sys tem of Vibrio fischeri, 383–385reg u la tory con trol, 430

Rabbit il eal loop model, di ar rheal dis ease, 38Rac, 540Ramoplanin, 418Rational de sign, new an ti bi ot ics by, 411Rational drug de sign, 412RCSB PDB (Research Collaboratory for Structural Bioinformatics

Protein Data Bank), 103R do main, 317Reactive ox y gen and ni tro gen spe cies, re sis tance to, 285–286Recipient, 165, 347Recipient cell, 163Recombinant DNA tech nol ogy, 204Recombinant genes, screen ing us ing, 208Recombinant pro teins, 206Recommended im mu ni za tion sched ules, 491Red fluo res cent pro tein (RFP), 231Regulation. See Virulence reg u la tionRegulator, 362Regulon, 362Reporter fu sions, 208–210Reporter genes, 208

com monly used sys tems, 211or ga ni za tion of sys tem, 210

Repressors, 454Reservoir hy poth e sis, 126, 128, 132Reservoirs, 166, 482Resfams (Resistance Families), 441ResFinder (Resistance Finder), 441Resident microbiota, 28Resistome, 441, 442Respiratory burst, 55Respiratory tract

de fenses of, 36–37path o gens, 37up per and lower, 37

Response reg u la tor, 364Restriction en zyme, 173Restriction-modification (RM) sys tems, 173, 174Retrospective study, 185RGD tags, 497Rhamnolipids, 562Rheumatoid ar thri tis, 13Rho, 540Rho (ρ) fac tor, 369Rhodamine, 196Rho-dependent ter mi na tors, 369Rhodospirillum, mo til ity, 262Rho-independent ter mi na tors, 369Ribosomal Database (RDB), 103Ribosome pro tec tion, 451Riboswitches, 369, 373Rice-water stool, 325Rickettsia, 280Rickettsia rickettsii, 567Rifampin (ri fam pi cin), 426–427

in hib it ing DNA and RNA syn the sis, 426re sis tance to, 452–453struc ture of, 427

RNA in ter fer ence (RNAi), 235, 236, 237RNA-seq, 17

RNA-seq pro fil ing, 118–120RNA-sequencing (RNA-Seq) tech nol ogy, 119, 216, 241, 242Rocky Mountain Laboratories, 206Rotavirus

rec om mended im mu ni za tion sched ule, 491side ef ects of vac cine, 493

Roux, Émile, 204Rubella, mor bid ity be fore and af ter vac cines, 488Ruminococcus sp., 35, 379RuvC, 238

Saccharomyces boulardii, 542Salmochelin, 555Salmonella spp., 11, 34, 38, 394

flu o ro quin o lones, 429path o gen evo lu tion, 177–178phase var i a tion, 159, 161, 162pili, 271re ac tive ox y gen spe cies in vac u ole, 287

Salmonella li po po ly sac cha ride (LPS), 303Salmonella Typhimurium, 142, 153, 229

ad her ence mech a nism, 269fac ul ta tive path o gen, 282, 283, 284

Salmonella bongori, path o ge nic ity is lands, 176, 178Salmonella enterica

mo til ity, 262path o ge nic ity is lands, 176screen ing, 208

Salmonella enterica serovar Typhi, 515Salmonella enterica serovar Typhimurium, 8, 576

dom i nant path o gen, 149lipid A moi ety from LPS of, 303model of host-pathogen-commensal mi crobe in ter ac tions, 247tu ber cu lo sis, 186

Salmonella typhi, 506Salmonella typhimurium, 219, 390Salmonellosis, 483Sandwich ELISA, 143, 145Sarin gas, 576SARS pan demic, 581, 585SCID (se vere com bined im mu no de fi cient) mice, 228, 229Screening

mu ta gen e sis, 210–214new an ti bi ot ics by, 411us ing re com bi nant genes, 208

SDS-PAGE (so dium dodecyl sul fate-polyacrylamide gel elec tro pho re sis), 243

Sebaceous glands, 28Sebum, 28SecA, 336SecB, 336Secondary me tab o lites, 258Secretion sys tems

cy to ly sin-mediated trans lo ca tion in S. pyogenes, 351–352Gram-negative, 339–340Gram-positive, 340ques tions, 354Sec-dependent, 338, 341Sec-independent, 341–350spe cial ized to Gram-positive bac te ria, 350–353sum mary of bac te rial, 339–340T1SS, 339, 341, 342T2SS, 338, 339, 341T3SS, 339, 341–347


IP: 54.70.40.11

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INDEX • 679

T4SS, 340, 347–348T5SS, 338, 339, 341, 342T6SS, 340, 348–350T7SS, 352–353

Secretory an ti bod ies, 78–79Secretory IgA (sIgA), 38, 41, 78–79

mu co sal im mu nity, 89–92struc ture, 75

Secretory IgA (sIgA) pro te ases, 264Secretory piece, 79Secretory sys tems

ac ces sory se cre tory (Sec) sys tem, 336cotranslational sig nal-recognition par ti cle (SRP) sys tem,

336–337gen eral se cre tory (Sec) sys tem, 336twin-arginine trans port (TAT) sys tem, 337–338

SecYEG, 336SEED, 103Select agents, 576, 578Selectins, 63Self an ti gen, 49Self-transmissible plas mids, 166, 461Semisynthetic an ti bi ot ics, 410Semmelweis, Ignaz, 30, 136Sensor his ti dine ki nases (SHK), 365, 366Sepsis, 4, 67Septicemia, 66Septic shock, 14, 66–69, 302Serotonin, 78Serotyping, 550Serratia marcescens, 31Serum an ti bod ies, 76–78

IgD, 78IgE, 78IgG, 76–77IgM, 77–78

Serum re sis tant, 60, 278Serum sen si tive, 60Severe sep sis, 67Sexually trans mit ted dis ease (STD), syph i lis, 141Shiga, Kiyoshi, 301Shiga-like tox ins (SLTs), 302, 553Shiga toxin (STx), 301, 313, 551Shiga toxin (STx-producing E. coli (STEC), 553Shiga tox in-producing E. coli (STEC), 553Shiga tox ins, 297Shigella, 177, 195, 354Shigella dysenteriae, 301, 551Shigella sonnei, dys en tery, 115, 116Short in ter fer ing RNA (siRNA), 235Sialic acid, 277Sialyltransferase, 161Siderophores, 266, 268sIgA. See Secretory IgA (sIgA)Sigma fac tors, 368–369Signal-recognition par ti cle (SRP) com plex, 337Signal se quence, 336Simple ep i the lium, 26Single guide RNA (sgRNA), 238Single nu cle o tide po ly mor phisms (SNPs), 158, 231, 233–234Site-specific recombinase (integrase), 462Skin

de fenses of, 27, 31–32in fec tion with com men sal bac te ria, 28

microbiota of, 124struc ture of, 25

Skin and mu co sade fenses of gas tro in tes ti nal tract, 34–36de fenses of mu co sal sur faces, 32–34de fenses of re spi ra tory tract, 36–37de fenses of skin, 31–32de fenses of uro gen i tal tract, 36im mune de fenses of, 37–38lay ers of cells pro tect ing body, 24–27mem brane bar ri ers, 24–37nor mal microbiota of, 27–29, 31

Skin-associated lym phoid tis sue (SALT), 37Skin microbiota, 124Slipped-strand misrepair, 160Slipped-strand syn the sis, 160Small in tes tine and co lon, microbiota of, 125–126, 128Small MASP-associated pro tein (sMAP), 61Smallpox, 577, 591

bioterror agent, 583erad i ca tion, 478mor bid ity be fore and af ter vac cines, 488

Small Rho GTPases, 540Small RNAs (sRNAs), 372, 374–375SNAP25, 321SNARE pro teins, 321Sneathia, microbiomes of new born in fants, 123Sneathia sanguinegens, phy lo ge netic trees, 105Snow, John, 144, 146, 204Somatic hypermutation, 76Somnolence, 66Sortases, 520, 521Specialized trans duc ing phages, 171Specific-pathogen-free (SPF), 148Specific-pathogen-free (SPF) an i mals, 188, 228Spectrum of ac tiv ity, an ti bi ot ics, 407, 408Spirochetes, 107Spontaneous gen er a tion, 136Spontaneous mu ta tion, ge netic change, 158–159Squalene, 495Squamous ep i the lium, 26Staphylococcal cas sette chro mo some mec (SCCmec), 523Staphylococcal en tero toxin (SE), 517Staphylococci

bac te rial in ter fer ence, 387bac te rial in ter fer ence of, 386

Staphylococcus sp., 35, 104, 123Staphylococcus au re us, 114, 178, 435, 515

Agr sys tem of, 385, 387an ti bi otic re sis tance, 439, 522–523cell sur face pro teins of, 265com par i son to S. epidermidis, 526–527ESKAPE, 440evad ing im mune sys tem, 264Gram-positive bac te rial sortases, 521met a bolic sens ing and vir u lence reg u la tion in, 365as op por tun ist, 516–524oro pha ryn geal microbiota, 125quo rum-sensing autoinducers, 379reg u la tion of vir u lence, 524re spi ra tory tract, 37stages of in fec tion and ab scess for ma tion, 518staphylokinase ac ti va tion of fi bri no lytic sys tem, 519Synercid, 432


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680 • INDEX

Staphylococcus au re us (continued )toxic shock syn drome by su per ab sor bent tam pon, 517tox ins, 517, 519–520vir u lence fac tors, 518, 520, 522

Staphylococcus epidermidis, 28, 29, 30–31, 225an ti mi cro bial pep tide sen sor Aps reg u la tory sys tem in, 526biofilm for ma tion and ef ects on im mune eva sion in, 524com par i son to S. au re us, 526–527CRISPR-Cas, 527fac tors con trib ut ing to col o ni za tion and path o gen e sis of, 525as op por tun ist, 288, 524–527plas tic im plants, 289skin microbiota, 124vir u lence fac tors, 525–526

Staphylococcus saprophyticus, 36Staphyloferrin, 364Staphylokinase, 288, 519Staphyloxanthin, 364Stem cell, 44Stem-loop struc tures, 454Stenotrophomonas maltophilia, 105Stochastic pro cesses, 459Stomach ul cers and can cer, 6Stratified ep i the lium, 26Streptococcus spp., 35, 104, 123Streptococcus agalactiae, 542Streptococcus gordonii, pili, 273Streptococcus mutans, cap sule com po si tion, 278Streptococcus oralis, pili, 273Streptococcus parasanguis, pili, 273Streptococcus pneumoniae, 6, 109, 163, 178, 186, 222, 242, 306

an ti bi otic re sis tance, 534bac te rial pneu mo nia, 278–279cap sule com po si tion, 278“Captain of all the men of death”, 527col o ni za tion and vir u lence fac tors, 529–534con trol by pneu mo coc cal vac ci na tion, 528es cap ing phagosome, 281in fec tions, 528nat u ral trans for ma tion in, 166as op por tu nis tic path o gen, 527–534pat tern rec og ni tion sig nal ing re cep tors and path ways

in in fec tion, 532pili, 273re spi ra tory tract, 37se quenc ing, 109–110steps in in va sive in fec tion, 533tis sue cul ture, 193trans for ma tion, 164–165vac cines, 528–529vir u lence fac tors of, 530vir u lence reg u la tion, 534

Streptococcus pyogenes, 171, 306, 515, 542cap sule, 277cap sule com po si tion, 278cy to ly sin-mediated trans lo ca tion in, 351–352evad ing im mune sys tem, 264re spi ra tory tract, 37

Streptococcus salivarius, pili, 273Streptogramin(s), 432, 452Streptogramin acetyltransferases, en zy matic in ac ti va tion of, 448Streptokinase, 519Streptolysin O (SLO), 351Streptomyces rapamycinicus, 413

Streptomycinevo lu tion of re sis tance, 438re sis tance to, 452–453

Structure-activity re la tion ships (SARs), 410Subacute bac te rial en do car di tis, 261Subcellular frac tion ation, 345Substrate, 192Subunit vac cines, 485, 488, 490Sulbactam, 448Sulfonamides, 429

evo lu tion of re sis tance, 438re sis tance to, 453struc ture and ac tion of, 428

Super-antigens, 85, 299, 300, 306Superantigens (Type I tox ins), 304–306Superbugs, 178, 442, 567Superoxide dis mut ase, 55Superoxide rad i cal, 55Suppurative, 65Supragenome, 178Surveillance pro grams, early warn ing sys tem, 11–12Survival curve anal y sis, 189–190Swiss-Prot (Swiss Institute of Bioinformatics), 103SYBR green, 107Synercid, 432Syntaxin, 321Synteny, 158Synthetic an ti bi ot ics, 410–412Syphilis, 141, 150, 262

Koch’s pos tu lates, 151Tuskegee ex per i ment, 184, 185

Systemic in flam ma tory re sponse syn drome (SIRS), 67Systems ge net ics, 231

T4SS-mediated DNA con ju ga tion, 174TALENs, 237, 238Tannerella for syth ia, 125, 133, 148, 511, 512Taxa, 101Taxon, 101Taxonomic unit, 104T-boxes, 369, 371T cell epi topes, 82T-cell-independent an ti body re sponses, 89T-cell-independent pro duc tion of an ti bod ies, 89T cell re cep tor (TCR), 81T cell re cep tor (TCR) com plex, 85T-cells, 91

im mu nity and mem ory, 86or gan isms, 93

T do main, 302Teichoic ac ids (TAs), 525Teicoplanin, 418, 420, 421Telithromycin, 424, 429Temperate phages, 171Tetanus, 322

mor bid ity be fore and af ter vac cines, 488Tetanus neu ro toxin (TeNT), 301Tetracycline(s), 423–424, 438

en zy matic in ac ti va tion of, 448, 450–451evo lu tion of re sis tance, 438mech a nisms of re sis tance, 450reg u la tion of re sis tance genes, 455re sis tance to, 451struc ture of, 423


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INDEX • 681

Tetracycline destructases, 448Tetrahydrofolic acid, 428, 429Tetrahymena, sur vival, 258Th2 cells, 85, 88T helper (Th) cells, 73

me di ated im mu nity, 86–87Thermostable riboswitches, 372Thermotoga maritima, 105Thiry-Vella loop, 90Thymus-dependent an ti gens, 87Tigecycline, struc ture of, 423Tight adherens junc tions, 24, 25Tight junc tions, 192Tissue cul ture mod els, 192–193Tissue fac tor (TF), 67Tissue pen e tra tion and dis sem i na tion, 288α-Tocopherol, struc ture of, 496Tolerance, 404

an ti bi otic re sis tance, 457, 459Toll, 51Toll-like re cep tor (TLR), 51, 52Totally drug-resistant Mtb (TDR-Mtb), 444Toxic ef ec tor pro teins, 299–300, 313Toxic fac tors, iso la tion and pu ri fi ca tion of, 204, 206Toxic shock, 66Toxic shock syn drome, 304, 517Toxic shock syn drome toxin (TSST), 304Toxic shock syn drome toxin 1 (TSST-1), 517α-Toxin, 301, 519Toxin A (TcdA), 537Toxin-antitoxin (TA) sys tems, 171, 173, 459–460Toxin B (TcdB), 537Toxin(s)

ques tions, 330–331re search tools, 327, 329toxin neu tral i za tion, 79see al so Bacterial tox in(s)

Toxoid(s), 295, 483Toxoid vac cines, 315Tracheal cy to toxin (TCT), 303, 304TracrRNA (trans-activating crRNA), 173, 238Transconjugants, 165Transcriptional ac ti va tors, 363, 456–457, 458Transcriptional fu sion, 208, 210Transcriptional re pres sors, 363Transcriptional re sponse (transcriptome), 240Transcription fac tors, 362Transcriptome, 17Transcriptomics, 101, 240–243

RNA-seq pro fil ing, 118–120Transcytosis, 90, 530Transduction, 171, 461Transfection, 235Transferrin, 43, 69, 266Transformants, 163Transformation, 461Transgenic an i mal(s), 227Transgenic an i mal mod els, 228–230Transgenic mice, 187, 228Transglycosylation, 421Translational at ten u a tion, 454, 456Translational fu sion, 208, 210Translation ini ti a tion, riboswitches, 373Translation reg u la tion, 374, 375

Translocase com plex, 336Translocation, 302Translocon, 310Transmigration, 47Transmission, 146Transpeptidation, 421Transposase, 463Transposase gene, 169Transposon(s), 169, 461

ba sic struc ture of, 462con ju ga tion with plas mids, 165–167, 169

Transposon in ser tion mu ta gen e sis, 212–214Transposon-sequencing (Tn-Seq) tech nol ogy, 214–216Treponema, 280Treponema denticola, 125, 148Treponema pallidum, 304

mo til ity, 262syph i lis, 141, 150, 151vi su al i za tion of, 140

2,4,5-Trichlorophenoxyacetic acid, 9Trichomonas vaginalis, met ro ni da zole, 426Triclosan, 406Trimethoprim, 429

re sis tance to, 453struc ture and ac tion of, 428

Triterpenoid-based ad ju vants, 495Tropheryma whipplei, 101Tropism, 270Tuberculosis, 87, 492, 506Tumorigenesis, en tero toxi genic Bacteroides

fragilis, 555Tumor ne cro sis fac tor al pha (TNF-α), 65Tuskegee syph i lis ex per i ment, 184, 185Twin-arginine trans port (TAT) sys tem, 337–338, 339Two-component reg u la tory sys tems (TCSs), 364–368Two-dimensional (2D) gel elec tro pho re sis, 243Tyndallization, 403Type 1 se cre tion sys tem (T1SS), 339, 341, 342Type 2 se cre tion sys tem (T2SS), 338, 339, 341Type 3 se cre tion sys tem (T3SS), 339, 341–347Type 4 se cre tion sys tem (T4SS), 340, 347–348Type 5 se cre tion sys tem (T5SS), 338, 339, 341, 342Type 6 se cre tion sys tem (T6SS), 340, 348–350Type 6 se cre tion sys tem (T6SS), 174Type 7 se cre tion sys tem (T7SS), 340, 352–353Type I hy per sen si tiv ity, 80Type II hy per sen si tiv ity, 80Type III hy per sen si tiv ity, 80Type IV hy per sen si tiv ity, 80Type V hy per sen si tiv ity, 80Type I tox ins, 302, 304–306Type II tox ins, 302, 306–307Type III tox ins, 302, 307, 309–313Typhoid, 136Typhoid fe ver, wa ter treat ment and in ci dence of, 402

Ubiquitin, 57Ulcers, stom ach, 6UniProt, 103UniProtKB (Universal Protein Resource Knowledgebase), 103United States Department of Agriculture (USDA), 11, 133, 291, 578,

582, 591United States Department of Health and Human

Services (HHS), 578


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682 • INDEX

University of Il li nois at Ur bana-Champaign, 581Ureaplasma parvum, 105Ureaplasma urealyticum, 105Urinary tract in fec tions (UTIs), 553Urogenital tracts, de fenses of, 36Uropathogenic E. coli (UPEC), 552, 553U.S. Army, 10U.S. Army Medical Research Institute of Infectious Diseases

(USAMRIID), 580U.S. Geological Survey, 224

Vaccination, 146, 478, 492Vaccine(s), 478

con ju gate vac cines, 490de liv ery of an ti gens as fu sions with bac te rial tox ins, 503diph the ria, 315dis ease mor bid ity be fore and af ter, 488ideal, 479–480im mu ni za tion pro grams, 480–485less-than-success sto ries, 492–494pas sive im mu ni za tion, 504rec om mended im mu ni za tion sched ules, 491re view of side ef ects, 486–487stor age of, 504Streptococcus pneumoniae, 528–529sub unit vac cines, 485, 488, 490suc cess sto ries, 485, 488–492

Vaccine de vel op ment, 494–503ad ju vants, 494–496en hanc ing im mu no ge nic ity, 494pro gram ming adap tive im mu nity, 496–500tar get ing mu co sal im mu nity, 500–503

Vaccine vec tor tech nol ogy, 500–502Vacuolating toxin (VacA), 302Vaginal-associated lym phoid tis sue (VALT), 90Vaginal Human Microbiome Project, 114Vaginal mi crobes, ra dial phy lo ge netic tree, 107Vaginal tract, microbiota of, 128, 129Vaginitis, 128Vaginosis, 128Valence, 80VAMP, 321Vancomycin, 418, 420

evo lu tion of re sis tance, 438mech a nisms of re sis tance, 453re sis tance, 463struc ture of, 420

Vancomycin-resistant Enterococcus (VRE), 452, 463Vancomycin-resistant S. au re us (VRSA), 452van Leeu wen hoek, Antonie, 136Variable re gion (Fv), 74Varicella, rec om mended im mu ni za tion sched ule, 491Variolation, 477Variola vi rus, 577Vasoactive, 64Vasodilation, 47V(D)J re com bi na tion, 76Veillonella, 35, 148Veillonella monpellierensis, 105Verotoxin, 301Vibrio, bio films, 259Vibrio alginolyticus, mo til ity, 262Vibrio anguillarum, 374Vibrio birdsii, 133, 223–224

Vibrio cholerae, 11, 133, 141, 150, 163, 164, 204, 223, 261, 515, 551, 584, 592

at tach ment to zoo plank ton and ma rine snow, 325chol era, 323, 325cul ture, 206fla gel lum, 261, 262path o ge nic ity is lands, 176quo rum-sensing autoinducers, 379strains ex press ing tox in-coregulated pili (TCP), 325ToxT reg u la tory net work in, 378virstatin against, 467

Vibrio fischeriLux sys tem of, 383–385Quorum-sensing sys tems of, 384

Vibrio parahaemolyticus, mo til ity, 262Vibrio vulnificus, 302Vi enna Ge ne ral Hospital, 30Viet nam War, 584Virginiamycin, 432Virosomes, 495–496, 497Virotyping, 551Virstatin, 430, 467Virulence, 152

bac te rial se cre tion sys tems and, 335–336gene ex pres sion, 257gene reg u la tion, 361

Virulence fac tor(s), 183–184, 255bio chem i cal ap proaches, 204, 206Clostridium dif cile, 537, 540con cept of, 313mo lec u lar ge netic ap proaches, 208–214op por tun ists, 288–289prom ise and cau tion, 247–248pro te o mics ap proaches for iden ti fy ing, 218–219Pseudomonas aeruginosa, 561–562, 563–564pu ri fi ca tion from bac te rial cul ture su per na tants, 205Streptococcus au re us, 518, 520, 522Streptococcus pneumoniae, 529–534sub acute bac te rial en do car di tis, 261

Virulence genescom par a tive ge no mic se quence anal y sis, 217–218ge nome-wide se quenc ing ap proaches, 214–218iden ti fy ing by clon ing and ex press ing them, 209trans po son in ser tion mu ta gen e sis, 212

Virulence reg u la tion, 361ac ti va tors and re pres sors, 362–364antiterminators, 369, 371, 372bac te rial chro ma tin, 375–376che mo taxis, 387–389global, 467mech a nisms of, 361–376op er ons, regulons and global reg u la tors, 362quo rum sens ing, 378–387reg u la tory small RNAs, 372, 374–375re spond ing to en vi ron men tal sig nals, 376–389sigma fac tors, 368–369Staphylococcus au re us, 524Streptococcus pneumoniae, 534tran scrip tional ter mi na tors, 369–370, 372trans la tion ini ti a tion, 372, 373two-component reg u la tory sys tems, 364–365, 367–368

Virulence traits, ac quir ing by hor i zon tal gene trans fer, 158

Visualization as say, re porter gene sys tems, 211


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INDEX • 683

Vitamin E, struc ture of, 496Von Beh ring, Emil, 204von Pettenkofer, Max J., 136, 142

Wall Street Journal (news pa per), 12Wal ter Reed mil i tary hos pi tal, 565War-related in fec tions, 10Warren, Robin, 142, 145, 154Waterborne in fec tions, 6, 7–8Weapon of mass de struc tion (WMD), 576Weapon of mass dis rup tion (WMD), 576Welch, Cur tis, 316Wells, H. G., 159Western blot, 332, 545Whip ple’s dis ease, 101White blood cells (leu ko cytes), 41Whitehead, 28Whole-body biophotonic im ag ing, 231Whole-genome se quenc ing

Shigella sonnei, 115, 116tech nol o gies, 109track ing mi crobes, 112, 114–115

Whooping cough (per tus sis), 304Wil liams, Anna Wessels, 204Willowbrook State School, 184Wil son, Brenda A., 581Wonder drugs, 401Wool-sorters dis ease, 582World Health Organization (WHO), 4, 478

World Trade Center, 9/11/2001, 576World War I, 10, 576Wound bot u lism, 320

XDR (ex ten sive ly-drug re sis tant), 567X-gal (indolyl-galactoside), 208X rays, 403

Yersin, Alexandre, 204Yersinia

ad her ence, 275path o gen e sis, 344

Yersiniabactin, 555Yersinia enterocolitica, 241Yersinia pestis, 10, 50, 243, 567

bioterror agent, 583–584path o ge nic ity is lands, 176reg u la tor of vir u lence, 373tran scrip tional ac ti va tor, 372

Yersinia pseu do tu ber cu lo sis, 92, 281YidC, 337Yops (Yersinia outer pro teins), 241

ZFNs (zinc-finger nu cle ases), 237, 238Ziehl, Franz, 139Zika pan demic, 581, 585Zinc-β-lactamases, 448Zoonotic, 482Zymogen, 51


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