Download Lecture 17 - Mechanisms of Pathogenecity Chpt. 17

6/10/2011
Mechanisms of Pathogenicity
The Microbes Fight Back
Medically important bacteria
Bacillus anthracis
Campylobacter
Clostridium botulinum
Clostridium difficile
Clostridium tetani
Corynebacterium diphtheriae
Enterococcus
Escherichia coli
ETEC
O157:H7
Mycobacterium tuberculosis
Neisseria gonorrhoeae
Pseudomonas aeruginosa
Salmonella
Shigella dysenteriae
Shigella sonnei
Staphylococcus aureus
Staph. epidermidis
Streptococcus pyogenes
(Group A)
Strep. pneumoniae
Treponema pallidum
Vibrio cholerae
Yersinia enterocolitica
Yersinia pestis
Eukaryotic parasites
Giardia species
Schistosoma species
Plasmodium species
Viruses
Herpes viruses
Influenza virus
Smallpox virus
Human immunodeficiency
virus
***this is not intended to be
a complete list****
Mechanisms of Pathogenesis
•Production of toxins that are then ingested
•Colonization of surface of the host, followed by toxin production
•Invasion of host tissues
•Invasion of host tissues followed by toxin production
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Mechanisms of Pathogenesis
•Production of toxins that are then ingested
•Colonization of surface of the host, followed by toxin production
•Invasion of host tissues
•Invasion
Invasion of host tissues followed by toxin production
“hit and run” versus persist
Establishment of Infection
Adherence
Adhesins
pili (fimbriae)
Establishment of Infection
Colonization (usually a mucous membrane)
Compete with normal microbiota
Obtain iron
siderophores
Avoid IgA
shed antigens (ex. pili)
(IgA protease)
antigenic variation
Y
Y
Y
Y
Y
Y
Y
Y
Y
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Establishment of Infection
Delivery of effector molecules to host cells
Type III secretion systems (injectisomes)
Establishment of Infection
Delivery of effector molecules to host cells
Type III secretion systems (injectisomes)
actin
Invasion - Breaching the
Anatomical Barriers
Penetration of skin
Penetration of mucous membranes
Directed uptake by an epithelial cell
injectisome
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Invasion - Breaching the
Anatomical Barriers
Penetration of skin
Penetration of mucous membranes
Directed uptake by an epithelial cell
Exploitation of antigen-sampling processes
Intestinal space (lumen)
M
P
Invasion - Breaching the
Anatomical Barriers
Penetration of skin
Penetration of mucous membranes
Directed uptake by an epithelial cell
Exploitation of antigen-sampling processes
Avoiding the Host Defenses
Hide within a host cell
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Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Gram-positives are protected by cell wall architecture
Gram-negative - some are “serum resistant”
Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Gram-positives are protected by cell wall architecture
Gram-negative - some are “serum resistant”
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Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Avoid destruction by phagocytes
Avoiding the Host Defenses
Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Avoid destruction by phagocytes
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Avoiding the Host Defenses
Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Avoid destruction by phagocytes
Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Avoid destruction by phagocytes
Figure 19.5
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Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Avoid destruction by phagocytes
Avoiding the Host Defenses
Hide within a host cell
Avoid killing by complement proteins
Avoid destruction by phagocytes
Avoid antibodies
Shed antigen
(IgA protease)
Antigenic variation
Mimic “self”
Damage to the Host
Exotoxins (toxins) - toxic proteins produced by bacteria; often described
according to their activity; neurotoxin, enterotoxin, cytotoxin
Proteins
Antigenic (vaccines can often be produced against them; toxoids)
Heat-labile (generally)
A B toxins (A subunit - active; B subunit - binds)
A-B
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Examples of exotoxin-producing bacteria
Examples of exotoxin-producing bacteria
Examples of exotoxin-producing bacteria
Clostridium tetani (neurotoxin)
tetanus
•obligate anaerobe, spore-former, soil, Gram-positive
•disease scenario/characteristics
•puncture wound → spores in tissue → germinate;
vegetative cells multiply
multiply, produce toxin
•toxin - blocks inhibition of motor reflexes (blocks nerve
transmission) → rigid contraction
•treatment - antitoxin, antibiotics
•prevention - vaccine; booster every 10 years
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Examples of exotoxin-producing bacteria
Corynebacterium diphtheriae (cytotoxin) diphtheria
Gram-positive rod, non-spore-forming, facultative
Examples of exotoxin-producing bacteria
Examples of exotoxin-producing bacteria
Corynebacterium diphtheriae (cytotoxin) diphtheria
•Colonizes throat
•Toxin - inhibits eukaryotic protein synthesis → cell death
•Local damage → pseudomembrane (dead cells, pus, blood)
•Systemic damage - organs (ex. heart)
•Lysogenic conversion
•Treatment - antitoxin, antibiotics (but still 10% fatality)
•Prevention - vaccine
•kids - DTaP; then booster every 10 yrs. (Td)
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Endotoxin
LPS (outer leaflet of Gram-negative outer membrane)
Triggers toll-like receptors, initiating inflammation
Localized - helps clear an infection
Systemic - can lead to shock
→dramatic drop in blood pressure,
disseminated intravascular
coagulation
Heat stable
No vaccine
Damaging effects of the immune response
Damage associated with inflammation
repair process → scarring
(ex. scarring of fallopian tubes → infertility)
Damage associated with antibodies
Antigen-antibody complexes (“immune complexes”)
activate complement → inflammation
Cross-reactive antibodies (i.e. bind to “self”)
→ autoimmune responses
Example of a highly successful pathogen:
Neisseria gonorrhoeae
•causes gonorrhea
•humans are the only host
•does not survive in the environment
•sexually transmitted
Asymptomatic infections
~ 50% of infected women
~ 10% of infected men
Gram-negative
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Example of a highly successful pathogen:
Neisseria gonorrhoeae
•causes gonorrhea
•humans are the only host
•does not survive in the environment
•sexually transmitted
Asymptomatic infections
~ 50% of infected women
~ 10% of infected men
Example of a highly successful pathogen:
Neisseria gonorrhoeae
Pathogenesis
•pili
attach to mucosal surfaces
hitch a ride on sperm?
p
•antigenic variation
multiple genes that encode pili
(other structures)
•(IgA protease)
Gram-negative
•invades epithelial cells
•appears to survive within neutrophils (PMNs)
Example of a highly successful pathogen:
Neisseria gonorrhoeae
Damage
•Inflammatory response
ascend fallopian tubes
→ Pelvic Inflammatory
y Disease
(PID)
scarring → infertility
Gram-negative
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