Module 9 Pathogenicity - Laulima...Figure 15.9 Microbial Mechanisms of Pathogenicity. When the...

© 2013 Pearson Education, Inc.

Module 9 Pathogenicity

© 2013 Pearson Education, Inc. Lectures prepared by Christine L. Case

Chapter 15

Microbial Mechanisms of Pathogenicity

© 2013 Pearson Education, Inc. Lectures prepared by Helmut Kae


Microbial Mechanisms of Pathogenicity

§  Pathogenicity: the ability of a pathogen to cause a disease by overcoming the defenses of the host

§  Virulence: the degree or extent of pathogenicity

§  A pathogenic organism is able to cause a disease §  A pathogen that is highly virulent causes damaging

disease


Portals of Entry

§  Portals of entry: avenues that pathogens can use to gain entry into the human body §  Mucous membranes §  Skin §  Parenteral route


Mucous membranes

§  Respiratory tract, gastrointestinal (GI) tract, genitourinary (GU) tract, conjunctiva

§  Most common portals are respiratory, GI tracts §  Inhaled through mouth, nose §  Eaten - most killed by acid, bile

§  GU tract is portal for pathogens that cause STDs


Skin

§  Largest organ, first line of defense §  Unbroken skin is impenetrable to most microbes

§  Some gain access through openings in skin §  Some fungi can infect skin directly


Parental Route

§  Access through breaks in skin §  From cuts, bites, drying

§  All microbes have preferred portal of entry §  Some microbes have multiple portals of entry


Numbers of Invading Microbes

§  Likelihood of disease increases as number of pathogens increase §  Too few can be overwhelmed by immune system



§  Virulence of a disease expressed as ID50: infectious dose for 50% of the test population

§  Expression of relative virulence under experimental conditions – can be different for different portals

§  Bacillus anthracis has 3 portals of entry

Portal of Entry ID50 Parenteral Route 10-50 endospores

Inhalation 10,000-20,000 endospores

Ingestion 250,000-1,000,000 endospores



§  Potency of toxin expressed as LD50: lethal dose for 50% of the test population

Toxin LD50 in mice Botulinum toxin 0.03 ng/kg

Shiga toxin 250 ng/kg

Staphylococcal enterotoxin 1350 ng/kg


Virulence Factors

§  Structures of molecules that a pathogen uses to cause disease

§  Many different virulence factors exist


Adherence

§  Means of attachment §  Necessary for pathogenicity in most pathogens §  Interfere with binding, interfere with infection

§  Adhesins (ligands) bind to complementary receptors §  Adhesins may be located on glycocalyx, surface

structures §  Adhesins usually glycoproteins, lipoproteins §  Binding is specific for certain host tissues, receptors


Figure 15.1a Adherence.

Surface molecules on a pathogen, called adhesins or ligands, bind specifically to complementary surface receptors on cells of certain host tissues.

Adhesin (ligand)

Host cell

surface

Receptor

Pathogen


How Pathogens Penetrate Host Defenses

§  Pathogens must penetrate tissue to cause disease §  Several factors contribute to the ability of pathogens

to invade a host


Capsules

§  Capsules impair phagocytosis (being eaten) §  Prevents binding to pathogen §  Capsules do not mean a bacterium is virulent


Cell Wall Components

§  Some cell walls contain chemicals that contribute to virulence

§ M protein resists phagocytosis § Streptococcus pyogenes

§ Opa protein inhibits T helper cells § Neisseria gonorrhoeae

§ Mycolic acid (waxy lipid) resists digestion § Mycobacterium tuberculosis


Enzymes

§  Coagulase: coagulates fibrinogen §  Kinases: digest fibrin clots §  Hyaluronidase: hydrolyzes hyaluronic acid §  Collagenase: hydrolyzes collagen §  IgA proteases: destroy IgA antibodies


Antigenic Variation

§  During pathogenesis, body produces antibodies to fight infection §  Bind to antigens on surface of bacteria

§  Antigenic variation: ability to alter surface antigen §  Changes slowly over time

§  By the time body produces antibodies, surface antigen has changed

§  Influenzavirus, N. gonorrhoeae, Trypanosoma brucei (African sleeping sickness)


How Bacterial Pathogens Damage Host Cells

§  Bacteria can damage host by: §  Using host’s nutrients §  Direct damage §  The production of toxins


Using Host’s Nutrients

§  Siderophores: proteins that tightly bind iron §  Iron is required for growth

§  Iron in human body is tightly bound

§  Some pathogens release siderophores to take away iron


Direct Damage

§  A number of ways that microbes can damage cells §  Grow within cells, multiply and rupture cell §  Attach to host cell and cause damage as pathogen uses

host for nutrients §  Penetrate hosts by secreting enzymes


Toxins

§  Toxins: poisonous substances that are produced by some microbes

§  Toxigenicity: ability of microbes to produce toxins §  Two types of toxins

§  Endotoxins §  Exotoxins


Exotoxins

§  Exotoxins: protein toxins made inside bacterium and secreted to its surroundings

§  Many are enzymes, so small amounts harmful §  Can act over and over again

Exotoxin: toxic substances released outside the cell

Clostridium botulinum, an example of a gram-positive bacterium that produces exotoxins


Exotoxins

§  Soluble in body fluids, can be transported all over body

§  Diseases caused by bacteria that produce toxins are a direct result of toxin §  Staphylococcal food poisoning is an intoxication

§  Antitoxins: antibodies produced by the body that provide immunity to toxins


Types of exotoxins

§  A-B toxins: consist of two parts, “A” and “B”

§  A part is active (enzyme) component

§  B part is the binding component

§  Diptheria toxin is A-B toxin


§  Lyse host cells by making protein channels in the plasma membrane – Leukocidins – Hemolysins – Streptolysins

§ Disrupts phospholipid bilayer

Membrane Disrupting Toxins


Superantigens

§  Provoke very intense immune response §  Stimulate proliferation (division) of T cells §  Release chemicals, cytokines, that regulate immune

response §  Too many cytokines in blood à fever, shock, death


Endotoxins

§  Part of cell wall of gram-negative bacteria §  LPS portion of outer membrane §  Endotoxin is the lipid portion, called Lipid A

Exotoxins are proteins, Endotoxins are lipids


Endotoxins

§  Endotoxins are released when Gram-negative bacteria die and cells lyse §  Liberates endotoxins §  Antibiotics can cause lysis à release LPS

Intact cell Dead cell

Endotoxins: toxins composed of lipids that are part of the cell membrane


Endotoxins

§  All endotoxins produce the same signs and symptoms §  Chills, fever, weakness, aches, shock, death §  Disseminated intravascular clotting

§  Shock: life threatening drop in blood pressure §  Endotoxic shock: shock produced by Gram-

negative bacterial endotoxin


Endotoxins

Endotoxins cause fever (by inducing the release of cytokines) and shock


Plasmids and Pathogenicity

§  R factors carry antibiotic resistance genes

§  Others can carry virulence factors §  Toxins – tetanus neurotoxin, staphylococcal enterotoxin

§  Fimbriae, adhesins, enzymes (coagulase)


Lysogeny and Pathogenicity

§  Prophage: phage DNA incorporated into bacterial chromosome

§  Prophage can provide new properties to bacteria

§  Lysogenic conversion: change in characteristics due to a prophage

§  Diptheria toxin, staphylococcal toxin, capsule of S. pneumoniae are encoded by prophages

§  Can transfer virulence genes to nonpathogenic strains


Figure 13.12 The lysogenic cycle of bacteriophage λ in E. coli.

Phage DNA (double-stranded)

Bacterial chromosome

Occasionally, the prophage may excise from the bacterial chromosome by another recombination event, initiating a lytic cycle.

Lysogenic cycle

Cell lyses, releasing phage virions.

Lytic cycle

New phage DNA and proteins are synthesized and assembled into virions.

Prophage

Many cell divisions

Lysogenic bacterium reproduces normally.

4A

Phage attaches to host cell and injects DNA.

5

4B

3B Phage DNA integrates within the bacterial chromosome by recombination, becoming a prophage.

1

2

3A

Phage DNA circularizes and enters lytic cycle or lysogenic cycle.

OR


Pathogenic Properties of Viruses

§  Viruses have a number of mechanisms to evade immune system §  Can grow inside of host cells §  Some can “hide” attachment sites - HIV has attachment sites too small for antibodies to

bind §  Some attack immune cells - HIV


Cytopathic Effects of Viruses

§  Cytopathic effects (CPE): visible effects of viral infection

§  CPE used to diagnose many viral infections


Figure 15.7 Some cytopathic effects of viruses.

Inclusion body

Cytoplasmic mass

Nuclei


Figure 15.8 Transformed cells in culture.


Cytopathic Effects of Viruses


Pathogenic Properties of Fungi

§  Fungal waste products may cause symptoms §  Chronic infections provoke an allergic response

§  Tichothecene: toxins that inhibit protein synthesis §  Fusarium, Stachybotrys

§  Proteases that modify host membranes, allow attachment §  Candida, Trichophyton

§  Capsule prevents phagocytosis. §  Cryptococcus


Pathogenic Properties of Protozoa

§  Presence of protozoa and their waste products often produce symptoms

§  Some (Plasmodium) invade host cells (red blood cells)

§  Others (Giardia lamblia) attach to host cells by a “sucking disc” and digest cells and tissue

§  Some undergo antigenic variation (Giardia, Trypanosomas)


Pathogenic Properties of Helminths

§  Presence of helminths causes disease §  Interferes with host function

§  Some (Wuchereria bancrofti) use host tissues for growth, reproduction (elephantitis) §  Block lymphatic circulation, leads to accumulation of

lymph, grotesque swelling


Pathogenic Properties of Algae

§  Some produce neurotoxins §  Paralytic shellfish poisoning

§  Alexandrium, a dinoflagellate


Portals of Exit

§  Specific route that microbes use to leave the body §  In secretions, excretions, discharges, tissue that’s been

shed

§  In general, portals of exit are related to infected tissue


§  Respiratory tract §  Coughing and sneezing

§  Gastrointestinal tract §  Feces and saliva

§  Genitourinary tract §  Urine and vaginal secretions

§  Skin §  Blood

§  Arthropods that bite; needles or syringes

Portals of Exit


Figure 15.9 Microbial Mechanisms of Pathogenicity.

When the balance between host and microbe is tipped in favor of the microbe, an infection or disease results. Learning these mechanisms of microbial pathogenicity is fundamental to understanding how pathogens are able to overcome the host’s defenses.

portals of entry

penetration or evasion of host defenses

damage to host cells portals of exit

Mucous membranes • Respiratory tract • Gastrointestinal tract • Genitourinary tract • Conjunctiva

Skin Parenteral route

Capsules Cell wall components Enzymes Antigenic variation Invasins Intracellular growth

Siderophores Direct damage Toxins

• Exotoxins • Endotoxins

Lysogenic conversion Cytopathic effects

Generally the same as the portals of entry for a given microbe: • Mucous membranes • Skin • Parenteral route

Number of invading microbes

Adherence

Clostridium tetani

Mycobacterium intracellulare

Micrographs are not shown to scale.

H1N1 flu virus

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