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GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture 33. Faculty: Dr. Alvin Fox. Key Words. Pathogen Transmission Outbreak, Epidemic, Pandemic Adhesion Normal flora Penetration Infection Invasiveness/spread
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GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture 33 Faculty: Dr. Alvin Fox
Key Words Pathogen Transmission Outbreak, Epidemic, Pandemic Adhesion Normal flora Penetration Infection Invasiveness/spread Infectious diseases Extra/intra cellular pathogen Compromised host Exotoxin Opportunistic infection Endotoxin - non-specific immunity Nosocomial Specific immunity Koch’s postulates Autoimmunity Bioterrorism
Pathogenicity • virulence factors • number of initial organisms • immune status
Pathogens • The “usual” rate • Oubreak - local • Epidemic - regional/national • Pandemic – widespread (international) • infections “beyond the norm”
Koch's postulates • isolated • diseased not healthy people • growth • pure culture • induce disease • susceptible animals • re-isolated • susceptible animals
Opportunistic infections • normal flora • environment • often compromised individuals
Opportunists - normal flora • Skin • Staphylococcus aureus • Staphylococcus epidermidis • Propionibacterium acnes • Intestine • Bacteroides • high numbers • Enterobacteriaceae • low number
Opportunists - environment • air • water • soil • food
Opportunists • Community-acquired • Nosocomial - hospital
Transmission • airborne droplets • food • water • sexual contact
Host defenses • Gut • peristalsis • defecation • respiratory tract • ciliary action • coughing • sneezing • urogenital tract • urination
Adhesion BACTERIUM adhesin receptor EPITHELIUM
S. pyogenes F-protein lipoteichoic acid fibronectin
E. coli Fimbriae Flagella
E. coli fimbriae Type 1 mannose P • galactose • glycolipids • glycoproteins
Penetration and spread Epithelium Blood stream Salmonella typhi Salmonella enteritidis Vibrio cholerae Gut lumen
Connective tissue destrction • Helps bacterial dissemination • collagenase • hyaluronidase
Extracellular pathogens • resistant to extra-cellular killing • killed on phagocytosis • resist killing • by avoiding internalization
Protein A inhibits phagocytosis PHAGOCYTE Fc receptor Protein A immunoglobulin BACTERIUM
r r r M protein inhibits phagocytosis Complement fibrinogen M protein peptidoglycan
Intracellular parasite Bacteria Macrophage or neutrophil Lysozome Phagosome Enter cytoplasm Fusion No fusion
Killing of intracellular parasite • Cell mediated immunity
Tissue Injury • exotoxins • endotoxins and non-specific immunity • - no antigen • specific immunity • - antigen
Exotoxins • proteins • usually enzymes • destroy cellular structures • destroy extracellular matrix
A-B toxins Cell surface Active Binding A B
Diphtheria toxin and Pseudomonas exotoxin A • ADP-ribosylates elongation factor (EF2) • inhibits protein synthesis • kills cells, destroys tissues
Cholera toxin and E. coli labile toxin • ADP-ribosylation of regulator • adenylate cyclase activation • cyclic AMP • active ion and water secretion • diarrhea
Shiga toxin - shigellosis • Shiga-like toxin – enterohemorrhagicE. coli • lyses 28S rRNA in ribosome • death of epithelial cells • poor water absorption • diarrhea
Botulinum toxin • inhibits acetylcholine release • inhibits nerve impulses • muscles inactive • flacid paralysis • Tetanus toxin • inhibits glycine release • inactivates inhibitory neurons • muscles over-active • rigid paralysis
Exotoxins - extracellular matrix of connective tissue • Clostridium perfringens • collagenase • Staphylococcus aureus • - hyaluronidase
Membrane damaging exotoxins • Proteases • Phospholipases • Detergent-like action
C. perfringens phospholipase • destroys blood vessels • stops influx inflammatory cells • creates anaerobic environment • allows growth of this strict anaerobe.
Exotoxins • Antibodies (anti-toxins) neutralize • vaccination
Endotoxin • Lipopolysaccharide - endotoxin • peptidoglycan -endotoxin-like action • cell envelope components • not proteins/enzymes
Septic shock • hypotension (tissue pooling of fluids) • disseminated intravascular coagulation • fever • lack of effective oxygenation • overall system failure
Endotoxins • non-specific inflammation • cytokine release • complement activation • B cell mitogens • polyclonal B cell activators • adjuvants
Specific immunity and immunopathology • chronic infection • tuberculosis • leprosy • syphilis • persisting bacterial remnants • autoimmunity
IgA proteases • help survival on external surfaces • H. influenzae • S. pneumoniae • N. gonorrhoeae • N. meningitidis
Bioterrorism • air • most common • no previous exposure • zoonoses • manifest initially • colds/flu-like • death or debilitation • recognition • clinically (e.g. common source clusters) • clinical microbiology • biodetection (environment) • future