Mechanisms of Pathogenicity

Transcription

1 Mechanisms of Pathogenicity The Microbes Fight Back Medically important bacteria Salmonella Bacillus anthracis Shigella dysenteriae Campylobacter Shigella sonnei Clostridium botulinum Staphylococcus aureus Clostridium difficile Staph. epidermidis Clostridium tetani Streptococcus pyogenes Corynebacterium diphtheriae (Group A) Enterococcus Strep. pneumoniae Escherichia coli Treponema pallidum ETEC Vibrio cholerae O157:H7 ersinia enterocolitica Mycobacterium tuberculosis ersinia pestis Neisseria gonorrhoeae Pseudomonas aeruginosa 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 1

2 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 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 2

3 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 3

4 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 4

5 Gram-positives are protected by cell wall architecture Gram-negative - some are serum resistant Gram-positives are protected by cell wall architecture Gram-negative - some are serum resistant 5

6 Avoid destruction by phagocytes Avoid destruction by phagocytes 6

7 Avoid destruction by phagocytes Avoid destruction by phagocytes Figure

8 Avoid destruction by phagocytes Avoid antibodies Shed antigen (IgA protease) Antigenic variation Mimic self Avoid destruction by phagocytes 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) 8

9 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, produce toxin toxin - blocks inhibition of motor reflexes (blocks nerve transmission) rigid contraction treatment - antitoxin, antibiotics prevention - vaccine; booster every 10 years 9

10 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) 10

11 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 11

12 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? antigenic variation multiple genes that encode pili (other structures) (IgA protease) invades epithelial cells appears to survive within neutrophils (PMNs) Gram-negative Example of a highly successful pathogen: Neisseria gonorrhoeae Damage Inflammatory response ascend fallopian tubes Pelvic Inflammatory Disease (PID) scarring infertility Gram-negative 12