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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

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Mechanisms of microbial disease l.jpg

Mechanisms of microbial disease

Schaechter et al, Chapter 9

Burton & Engelkirk Chapter 7


Microbe is extracellular l.jpg

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


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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


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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


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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


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Microbe invades cell

  • Cell membrane weakened by enzymes

  • Fimbriae/pili allow attachment to cell wall – confers specificity for cell types


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Microbe invades cell

  • Cell membrane weakened by enzymes

  • Fimbriae/pili allow attachment to cell wall – confers specificity for cell types


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Intracellular

  • Host cell killed:

  • Lysis during replication

  • Necrosis

  • Apoptosis

  • Immune system attacks infected cells


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The cell cycle

Apoptosis, programmed cell death

A

G1

G0

S

M

G2

Mitosis (Cell division)


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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


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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”


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Rat fibroblasts


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Renewal by duplication - proliferation

eg endothelial cells

pancreas

hepatocytes ?

Renewal by differentiation of stem cells

eg skin, intestinal wall, blood cells

Cell renewal


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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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