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Lecture 6

Lecture 6 Notes

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Biomedical Sciences
John Bertram

Lecture 6 Notes: Mechanisms of bacterial pathogenesis: Lecture objectives:  To understand some of the major mechanisms whereby bacterial pathogens damage the host  To know the differences between different types of bacterial toxins  To understand the differences between the direct and indirect effect of toxins  To understand the mechanisms whereby bacterial toxins cause damage in the host  To have an understanding of the major genetic mechanisms by which bacteria can become pathogenic To cause disease most pathogens must: 5) cause damage to the host Damage to host (disease): Effect of bacterial toxins: 1. Direct: e.g. secreted or cell-associated bacterial toxins – often called exotoxins 2. Indirect: microbial toxin overstimulates your immune response Direct:  Exotoxins: o Secreted proteins by bacteria and some fungi (called mycotoxins). Produced in cytoplasm and secreted from bacterial cell into extracellular space o Designated by:  Types of cell it attacks (e.g. cytotoxin, neurotoxin, cardiotoxin)  Types of cell that produces it (e.g. cholera toxin, shiga toxin)  Type of activity it produces (enterotoxin – responsible for gastroenteritis)  Endotoxin o Bacterial Lipopolysaccharide o Remain attached to the bacterial cell wall Bacterial exotoxins: 3 main types: 1. A-B toxins (e.g. cholera toxin) 2. Membrane disrupting toxins (contains pore-forming toxins – affect cell membrane of cells) 3. Superantigens (over-stimulate immune system) 1) A-B toxins: Structure:  A subunit has ADP-ribosylating activity which results in protein conformation changes of host cells which renders the proteins non-functional or causes them to behave differently  A-B toxins will always have an A and B subunit but compound A-B toxins have more B subunits  B subunit is solely responsible for binding the toxin to the host cell membrane and it mediates endocytosis which results in the internalisation of the toxin  Once the A subunit enters the cytoplasm it exerts its ADP-ribosylating activity   E.G diphtheria toxin: o Toxin gene carried on lysogenic bacteriophage o Simple – one A subunit and one B subunit  E.g. Cholera toxin: o Compound A-B toxin o  A-B neurotoxin: Botulinim toxin (botulism) o Attack the nerve cells of the diaphragm so you can't breathe, or in the heart muscles and cause cardiac arrest o o botulism toxin is resistant to acid in the stomach so can pass through and go into blood stream and attack nerves and cause paralysis & death o C. botulinum grows in GIT of infants as their normal flora hasn’t developed yet o Also grows in wounds  Bacterial infection is not essential for disease (botulism toxin gives you the disease NOT clostridium bostulinim)  2) Membrane
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