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Mechanisms of microbial disease. Schaechter et al, Chapter 9 Burton & Engelkirk Chapter 7. Microbe is Extracellular. Microbe secretes exotoxin Botulinus, tetanus toxin (neurotoxins) Enterotoxins (Cholera toxin, toxigenic E, coli, stimulate adenylate cyclase; Shigella toxin, cytotoxic;

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mechanisms of microbial disease

Mechanisms of microbial disease

Schaechter et al, Chapter 9

Burton & Engelkirk Chapter 7

microbe is extracellular
Microbe is Extracellular
  • Microbe secretes exotoxin
    • Botulinus, tetanus toxin (neurotoxins)
    • Enterotoxins (Cholera toxin, toxigenic E, coli, stimulate adenylate cyclase; Shigella toxin, cytotoxic;

E. coli O157:H7, both)

    • Hemolysin, leukocidin, lecithinase
  • Microbe secretes enzymes
    • Coagulase, kinases (fibrinolysin), hyaluronidase, collagenase
  • Microbial membrane elicits reaction
    • Endotoxin, the lipopolysaccharide of the outer membrane of Gram-negative bacteria
functional damage
Functional Damage
  • Biochemical changes in host cell
    • Ion leakage, fluid leakage
    • Cholera toxin, targets intestinal epithelia
    • Lytic pores, S. aureusα-toxin
  • Disruption/destruction of membrane
  • Inhibition of protein synthesis
    • Diphtheria, Pseudomonas aeruginosa
  • Inhibition of nerve function
    • Clostridium toxins, tetanus, botulinum
microbe is extracellular4
Microbe is Extracellular
  • Microbe secretes exotoxin
    • Botulinus, tetanus toxin (neurotoxins)
    • Enterotoxins (Cholera toxin, toxigenic E, coli, stimulate adenylate cyclase; Shigella toxin, cytotoxic;

E. coli O157:H7, both)

    • Hemolysin, leukocidin, lecithinase
  • Microbe secretes enzymes
    • Coagulase, kinases (fibrinolysin), hyaluronidase, collagenase
  • Microbial membrane elicits reaction
    • Endotoxin, the lipopolysaccharide of the outer membrane of Gram-negative bacteria
functional damage5
Functional Damage
  • Biochemical changes in host cell
    • Ion leakage, fluid leakage
    • Cholera toxin, targets intestinal epithelia
    • Lytic pores, S. aureusα-toxin
  • Disruption/destruction of membrane
  • Inhibition of protein synthesis
    • Diphtheria, Pseudomonas aeruginosa
  • Inhibition of nerve function
    • Clostridium toxins, tetanus, botulinum
microbe invades cell
Microbe invades cell
  • Cell membrane weakened by enzymes
  • Fimbriae/pili allow attachment to cell wall – confers specificity for cell types
microbe invades cell7
Microbe invades cell
  • Cell membrane weakened by enzymes
  • Fimbriae/pili allow attachment to cell wall – confers specificity for cell types
intracellular
Intracellular
  • Host cell killed:
  • Lysis during replication
  • Necrosis
  • Apoptosis
  • Immune system attacks infected cells
the cell cycle
The cell cycle

Apoptosis, programmed cell death

A

G1

G0

S

M

G2

Mitosis (Cell division)

apoptosis vs necrosis
APOPTOSIS

In response to defined signals

Follows defined sequence of events

“Orderly shut-down” of cell functions

Cell macromolecules recovered, recycled

NECROSIS

In response to non-specific damage

Often starts with membrane destruction, events thereafter unpredictable

Disorderly

No recovery of contents

Apoptosis vs necrosis
different cell types
Different cell types
  • Connective tissue, fibroblasts
  • Endothelial cells, lining of blood vessels
  • Epithelial cells, “outside” of several tissues
  • Hepatocytes, liver cells
  • Some cell populations are continually being renewed (turnover), others are “permanent”
cell renewal
Renewal by duplication - proliferation

eg endothelial cells

pancreas

hepatocytes ?

Renewal by differentiation of stem cells

eg skin, intestinal wall, blood cells

Cell renewal
cell reproduction cell development
Cell reproduction, cell development

“Generic” Specialized

Stem cells Differentiated cells

Pluripotent stem cells Different types of

differentiated cells

Totipotent (embryonic) stem cells Organs, organisms ?

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