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27.1 Overview of Human–Microbial Interactions Most microorganisms are benign –Few contribute to...
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Transcript of 27.1 Overview of Human–Microbial Interactions Most microorganisms are benign –Few contribute to...
27.1 Overview of Human–Microbial Interactions
• Most microorganisms are benign– Few contribute to health and fewer pose direct
threats to health
• Normal microbial flora– Microorganisms usually found associated with
human body tissue
• Humans are colonized by microorganisms at birth
© 2012 Pearson Education, Inc.
27.1 Overview of Human–Microbial Interactions
• Pathogens– Microbial parasites
• Pathogenicity– The ability of a parasite to inflict damage on
the host
• Virulence– Measure of pathogenicity
• Opportunistic pathogen– Causes disease only in the absence of normal
host resistance© 2012 Pearson Education, Inc.
27.1 Overview of Human–Microbial Interactions
• Infection– Situation in which a microorganism is established
and growing in a host, whether or not the host is harmed
• Disease– Damage or injury to the host that impairs host
function
© 2012 Pearson Education, Inc.
27.2 Normal Microflora of the Skin
• The skin is generally a dry, acid environment that does not support the growth of most microorganisms (Figure 27.2)
• Moist areas (e.g., sweat glands) are readily colonized by gram-positive bacteria and other normal flora of the skin– Composition is influenced by
• Environmental factors (e.g., weather) • Host factors (e.g., age, personal hygiene)
© 2012 Pearson Education, Inc.
27.3 Normal Microflora of the Oral Cavity
• The oral cavity is a complex, heterogeneous microbial habitat
• Saliva contains antimicrobial enzymes– But high concentrations of nutrients near
surfaces in the mouth promote localized microbial growth
• The tooth consists of a mineral matrix (enamel) surrounding living tissue (dentin and pulp; Figure 27.4)
© 2012 Pearson Education, Inc.
Figure 27.4
Enamel
Dentin
Gingival crevice
Pulp
Gingiva
Alveolar bone
Periodontalmembrane
Bonemarrow
Crown
Root
© 2012 Pearson Education, Inc.
Figure 27.5
© 2012 Pearson Education, Inc.
27.3 Normal Microflora of the Oral Cavity
• Extensive growth of oral microorganisms, especially streptococci, results in a thick bacterial layer (dental plaque)
• As plaque continues to develop, anaerobic bacterial species begin to grow
© 2012 Pearson Education, Inc.
Figure 27.6
Day 1 1436 mm2
Day 10 22,522 mm2
© 2012 Pearson Education, Inc.
Figure 27.7
© 2012 Pearson Education, Inc.
27.3 Normal Microflora of the Oral Cavity
• As dental plaque accumulates, the microorganisms produce high concentrations of acid that results in decalcification of the tooth enamel (dental caries)
• The lactic acid bacteria Streptococcus sobrinus and Streptococcus mutans are common agents in dental caries (Figure 27.8)
© 2012 Pearson Education, Inc.
27.4 Normal Microflora of the Gastrointestinal Tract
• The human gastrointestinal (GI) tract– Consists of stomach, small intestine, and large
intestine
– Responsible for digestion of food, absorption of nutrients, and production of nutrients by the indigenous microbial flora
– Contains 1013 to 1014 microbial cells
© 2012 Pearson Education, Inc.
Figure 27.9
Major bacteria present Organ
Esophagus
Stomach
Smallintestine
Largeintestine
pH 2
Secretion of acid (HCl)Digestion of macromolecules
pH 4–5
Continued digestionAbsorption of monosaccharides,amino acids, fatty acids, water
pH 7
Absorption of bile acids,vitamin B12
Duodenum
Jejunum
Ileum
Colon
Anus
Esophagus
LactobacilliEnterococci
PrevotellaStreptococcusVeillonella
HelicobacterProteobacteriaBacteroidetesActinobacteriaFusobacteria
BacteroidesBifidobacteriumClostridiumEnterobacteriaEnterococcusEscherichiaEubacteriumKlebsiellaLactobacillusMethanobrevibacter (Archaea)PeptococcusPeptostreptococcusProteusRuminococcusStaphylococcusStreptococcus
Major physiologicalprocesses
© 2012 Pearson Education, Inc.
27.4 Normal Microflora of the Gastrointestinal Tract
• Functions and Products of Intestinal Flora– Intestinal microorganisms carry out a variety of
essential metabolic reactions that produce various compounds
• The type and amount produced is influenced by the composition of the intestinal flora and the diet
• Compounds produced include:– Vitamins
– Gas, organic acids, and odor
– Enzymes
© 2012 Pearson Education, Inc.
27.5 Normal Microflora of Other Body Regions
• A restricted group of organisms colonizes the upper respiratory tract– Examples: staphylococci, streptococci,
diphtheroid bacilli, and gram-negative cocci
• The lower respiratory tract lacks microflora in healthy individuals
© 2012 Pearson Education, Inc.
Figure 27.11
Sinuses
Nasopharynx
Pharynx
Oral cavity
Larynx
Trachea
Bronchi
Lungs
Upperrespiratorytract
Lowerrespiratorytract
© 2012 Pearson Education, Inc.
27.5 Normal Microflora of Other Body Regions
• Urogenital Tract– The bladder is typically sterile in both males and
females
– Altered conditions (such as change in pH) can cause potential pathogens in the urethra (such as Escherichia coli and Proteus mirabilis) to multiply and become pathogenic
• E. coli and P. mirabilis frequently cause urinary tract infections in women
© 2012 Pearson Education, Inc.
27.5 Normal Microflora of Other Body Regions
• The vagina of the adult female is weakly acidic and contains significant amounts of glycogen – Lactobacillus acidophilus, a resident organism in
the vagina, ferments the glycogen, producing lactic acid
– Lactic acid maintains a local acidic environment
© 2012 Pearson Education, Inc.
27.6 Measuring Virulence
• Pathogens use various strategies to establish virulence (Figure 27.13)
• Virulence is the relative ability of a pathogen to cause disease
© 2012 Pearson Education, Inc.
27.6 Measuring Virulence
• Measuring Virulence– Virulence can be estimated from experimental
studies of the LD50 (lethal dose50)
• The amount of an agent that kills 50% of the animals in a test group
– Highly virulent pathogens show little difference in the number of cells required to kill 100% of the population as compared to 50% of the population
© 2012 Pearson Education, Inc.
Figure 27.14
Number of cells injected per mouse
101 102 103 104 105 106 107
100
80
60
40
20
Pe
rce
nta
ge
of
mic
e k
ille
d
Highly virulentorganism(Streptococcuspneumoniae)
Moderately virulentorganism(Salmonella entericaserovar Typhimurium)
© 2012 Pearson Education, Inc.
27.6 Measuring Virulence
• Attenuation– The decrease or loss of virulence
• Toxicity– Organism causes disease by means of a
toxin that inhibits host cell function or kills host cells
• Toxins can travel to sites within host not inhabited by pathogen
© 2012 Pearson Education, Inc.
Figure 27.13
EXPOSUREto pathogens
ADHERENCEto skin or mucosa
INVASIONthrough epithelium
COLONIZATIONand
GROWTHProduction of
virulence factors
TOXICITY:toxin effects arelocal or systemic
INVASIVENESS:further growth atoriginal and distant sites
TISSUEDAMAGE,DISEASE
Further exposure
Further exposure at local sites
© 2012 Pearson Education, Inc.
27.7 Entry of the Pathogen into the Host – Adherence
• Specific Adherence– A pathogen must usually gain access to host
tissues and multiply before damage can be done
– Bacteria and viruses that initiate infection often adhere specifically to epithelial cells through macromolecular interactions on the surfaces of the pathogen and the host cell (Figure 27.15)
© 2012 Pearson Education, Inc.
Figure 27.15
© 2012 Pearson Education, Inc.
27.7 Entry of the Pathogen into the Host – Adherence
• Bacterial adherence can be facilitated by – Extracellular macromolecules that are not
covalently attached to the bacterial cell surface• Examples: slime layer, capsule
– Fimbriae and pili
© 2012 Pearson Education, Inc.
Figure 27.16
© 2012 Pearson Education, Inc.
Figure 27.18
© 2012 Pearson Education, Inc.
27.6 Measuring Virulence
• Invasiveness– Ability of a pathogen to grow in host tissue at
densities that inhibit host function• Can cause damage without producing a toxin
• Many pathogens use a combination of toxins, invasiveness, and other virulence factors to enhance pathogenicity
© 2012 Pearson Education, Inc.
27.7 Entry of the Pathogen into the Host – Adherence
• Pathogen Invasion– Starts at the site of adherence
– May spread throughout the host via the circulatory or lymphatic systems
© 2012 Pearson Education, Inc.
27.8 Colonization and Infection
• The availability of nutrients is most important in affecting pathogen growth
• Pathogens may grow locally at the site of invasion or may spread throughout the body
© 2012 Pearson Education, Inc.
27.9 Invasion
• Pathogens produce enzymes that – Enhance virulence by breaking down or altering
host tissue to provide access to nutrients• Example: hyaluronidase
– Protect the pathogen by interfering with normal host defense mechanisms
• Example: coagulase
© 2012 Pearson Education, Inc.
27.10 Exotoxins
• Exotoxins– Proteins released from the pathogen cell as it
grows
– Three categories:• Cytolytic toxins• AB toxins• Superantigen toxins
© 2012 Pearson Education, Inc.
27.10 Exotoxins
• Cytolytic toxins– Work by degrading cytoplasmic membrane
integrity, causing cell lysis and death• Toxins that lyse red blood cells are called
hemolysins (Figure 27.19)• Staphylococcal -toxin kills nucleated cells and
lyses erythrocytes (Figure 27.20)
© 2012 Pearson Education, Inc.
Figure 27.19
© 2012 Pearson Education, Inc.
Figure 27.20
Cytoplasmicmembrane
-Toxin pore
Out
InInflux of extracellularcomponents
Efflux ofcytoplasmiccomponents
© 2012 Pearson Education, Inc.
27.10 Exotoxins
• AB toxins– Consist of two subunits, A and B
– Work by binding to host cell receptor (B subunit) and transferring damaging agent (A subunit) across the cell membrane (Figure 27.21)
• Examples: diphtheria toxin, tetanus toxin, botulinum toxin
© 2012 Pearson Education, Inc.
Animation: Diphtheria and Cholera ToxinsAnimation: Diphtheria and Cholera Toxins
Figure 27.21
Cytoplasmicmembrane
Diphtheria toxinAmino acid
Ribosome
Diphtheria toxin
Receptorprotein
Out
In
Normal protein synthesis Protein synthesis stops
© 2012 Pearson Education, Inc.
27.10 Exotoxins
• Clostridium tetani and Clostridium botulinum produce potent AB exotoxins that affect nervous tissue
• Botulinum toxin consists of several related AB toxins that are the most potent biological toxins known (Figure 27.22); tetanus toxin is also an AB protein neurotoxin (Figure 27.23)
© 2012 Pearson Education, Inc.
Figure 27.22
Excitation signalsfrom the centralnervous system
Muscle
NormalAcetylcholine (A) inducescontraction of muscle fibers
BotulismBotulinum toxin, , blocksrelease of A, inhibiting contraction
© 2012 Pearson Education, Inc.
Figure 27.23
Inhibitoryinterneuron
Inhibition
Excitation signalsfrom the centralnervous system
Tetanustoxin
Muscle
NormalGlycine (G) release from inhibitoryinterneurons stops acetylcholine(A) release and allows relaxationof muscle
TetanusTetanus toxin binds to inhibitoryinterneurons, preventing releaseof glycine (G) and relaxationof muscle
© 2012 Pearson Education, Inc.
27.10 Exotoxins
• Enterotoxins– Exotoxins whose activity affects the small
intestine
– Generally cause massive secretion of fluid into the intestinal lumen, resulting in vomiting and diarrhea
• Example: cholera toxin (Figure 27.24)
© 2012 Pearson Education, Inc.
Figure 27.24
Blood Intestinalepithelialcells
GM1
Lumen ofsmall intestine
Normal ion movement, Na from lumen to blood,no net Cl movement
Colonization and toxin production by V. cholerae
Activation of epithelial adenylate cyclase by cholera toxin
Na movement blocked, net Cl movement to lumen
Massive water movement to the lumen; cholera symptoms
CholeratoxinAB form
Vibriocholeraecell
GM1
A subunits
Adenylate cyclase
ATP Cyclic AMP
Choleratoxin Bsubunit
© 2012 Pearson Education, Inc.
27.11 Endotoxins
• Endotoxin– The lipopolysaccharide portion of the cell
envelope of certain gram-negative Bacteria, which is a toxin when solubilized
– Generally less toxic than exotoxins
– The presence of endotoxin can be detected by the Limulus amoebocyte lysate (LAL) assay (Figure 27.25)
© 2012 Pearson Education, Inc.
Figure 27.25
© 2012 Pearson Education, Inc.