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GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture 33 PowerPoint PPT Presentation


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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

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General aspects of bacterial pathogenesis lecture 33

GENERAL ASPECTS OF

BACTERIAL PATHOGENESIS

Lecture 33

Faculty: Dr. Alvin Fox


Key words

Key Words

PathogenTransmission

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

Pathogenicity

  • virulence factors

  • number of initial organisms

  • immune status


Pathogens

Pathogens

  • The “usual” rate

  • Oubreak - local

  • Epidemic - regional/national

  • Pandemic – widespread (international)

    • infections “beyond the norm”


Koch s postulates

Koch's postulates

  • isolated

    • diseased not healthy people

  • growth

    • pure culture

  • induce disease

    • susceptible animals

  • re-isolated

    • susceptible animals


Opportunistic infections

Opportunistic infections

  • normal flora

  • environment

  • often compromised individuals


Opportunists normal flora

Opportunists - normal flora

  • Skin

    • Staphylococcus aureus

    • Staphylococcus epidermidis

    • Propionibacterium acnes

  • Intestine

    • Bacteroides

      • high numbers

    • Enterobacteriaceae

      • low number


Opportunists environment

Opportunists - environment

  • air

  • water

  • soil

  • food


Opportunists

Opportunists

  • Community-acquired

  • Nosocomial - hospital


Transmission

Transmission

  • airborne droplets

  • food

  • water

  • sexual contact


Host defenses

Host defenses

  • Gut

    • peristalsis

    • defecation

  • respiratory tract

    • ciliary action

    • coughing

    • sneezing

  • urogenital tract

    • urination


Adhesion

Adhesion

BACTERIUM

adhesin

receptor

EPITHELIUM


S pyogenes

S. pyogenes

F-protein

lipoteichoic acid

fibronectin


General aspects of bacterial pathogenesis lecture 33

E. coli

Fimbriae

Flagella


E coli fimbriae

E. coli fimbriae

Type 1

mannose

P

  • galactose

    • glycolipids

    • glycoproteins


Penetration and spread

Penetration and spread

Epithelium

Blood stream

Salmonella typhi

Salmonella enteritidis

Vibrio cholerae

Gut lumen


Connective tissue destrction

Connective tissue destrction

  • Helps bacterial dissemination

    • collagenase

    • hyaluronidase


Extracellular pathogens

Extracellular pathogens

  • resistant to extra-cellular killing

  • killed on phagocytosis

  • resist killing

    • by avoiding internalization


Protein a inhibits phagocytosis

Protein A inhibits phagocytosis

PHAGOCYTE

Fc receptor

Protein A

immunoglobulin

BACTERIUM


M protein inhibits phagocytosis

r

r

r

M protein inhibits phagocytosis

Complement

fibrinogen

M protein

peptidoglycan


Intracellular parasite

Intracellular parasite

Bacteria

Macrophage or neutrophil

Lysozome

Phagosome

Enter cytoplasm

Fusion

No fusion


Killing of intracellular parasite

Killing of intracellular parasite

  • Cell mediated immunity


Tissue injury

Tissue Injury

  • exotoxins

  • endotoxins and non-specific immunity

    • - no antigen

  • specific immunity

    • - antigen


  • General aspects of bacterial pathogenesis lecture 33

    Exotoxins

    • proteins

    • usually enzymes

    • destroy cellular structures

    • destroy extracellular matrix


    A b toxins

    A-B toxins

    Cell surface

    Active

    Binding

    A

    B


    General aspects of bacterial pathogenesis lecture 33

    • Diphtheria toxin and Pseudomonas exotoxin A

      • ADP-ribosylates elongation factor (EF2)

      • inhibits protein synthesis

      • kills cells, destroys tissues


    General aspects of bacterial pathogenesis lecture 33

    Cholera toxin and E. coli labile toxin

    • ADP-ribosylation of regulator

    • adenylate cyclase activation

    • cyclic AMP

    • active ion and water secretion

    • diarrhea


    General aspects of bacterial pathogenesis lecture 33

    • Shiga toxin - shigellosis

    • Shiga-like toxin – enterohemorrhagicE. coli

    • lyses 28S rRNA in ribosome

    • death of epithelial cells

    • poor water absorption

    • diarrhea


    General aspects of bacterial pathogenesis lecture 33

    • 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


    General aspects of bacterial pathogenesis lecture 33

    Exotoxins - extracellular matrix of connective tissue

    • Clostridium perfringens

      • collagenase

    • Staphylococcus aureus

      • - hyaluronidase


    General aspects of bacterial pathogenesis lecture 33

    Membrane damaging exotoxins

    • Proteases

    • Phospholipases

    • Detergent-like action


    General aspects of bacterial pathogenesis lecture 33

    C. perfringens phospholipase

    • destroys blood vessels

    • stops influx inflammatory cells

    • creates anaerobic environment

    • allows growth of this strict anaerobe.


    Exotoxins

    Exotoxins

    • Antibodies (anti-toxins) neutralize

      • vaccination


    Endotoxin

    Endotoxin

    • Lipopolysaccharide - endotoxin

    • peptidoglycan -endotoxin-like action

    • cell envelope components

    • not proteins/enzymes


    General aspects of bacterial pathogenesis lecture 33

    Septic shock

    • hypotension (tissue pooling of fluids)

    • disseminated intravascular coagulation

    • fever

    • lack of effective oxygenation

    • overall system failure


    Endotoxins

    Endotoxins

    • non-specific inflammation

    • cytokine release

    • complement activation

    • B cell mitogens

    • polyclonal B cell activators

    • adjuvants


    Specific immunity and immunopathology

    Specific immunity and immunopathology

    • chronic infection

      • tuberculosis

      • leprosy

      • syphilis

  • persisting bacterial remnants

  • autoimmunity


  • General aspects of bacterial pathogenesis lecture 33

    IgA proteases

    • help survival on external surfaces

      • H. influenzae

      • S. pneumoniae

      • N. gonorrhoeae

      • N. meningitidis


    Bioterrorism

    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


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