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  Quiz (Ch. 33)
Quiz (Ch. 29)

Antimicrobial Chemotherapy. Nonspecific Host Defenses

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Last revised: Friday, April 21, 2000
Ch. 33; Ch. 20 (p. 591-602) in Prescott et al, Microbiology, 4th Ed.
Note: These notes are provided as a guide to topics the instructor hopes to cover during lecture. Actual coverage will always differ somewhat from what is printed here. These notes are not a substitute for the actual lecture!
Copyright 2000. Thomas M. Terry

Antimicrobial Drugs

So far, talked about agents applied outside body. Rise of chemotherapeutics was major revolution in medicine

A. History:

  1. Antibiotics known for long time= chemicals produced by certain organisms that killed other organism. E.g. mushroom poisons. Early searches for antibiotics (ca. 1900) had bad side-effects. People decided that therapeutic applications were probably too dangerous.
  2. Ehrlich's "magic bullet": 1909, discovered "Salvarsan", chemical used to treat syphillis. Ehrlich stressed Selective toxicity as key factor in success.

B. Structural analogues as drugs


C. Antibiotics:

1. Cell Wall antibiotics

2. Inhibitors of protein synthesis


D. Drug resistance

Testing for Drug Resistance

History:

Different ways for bacteria to develop drug resistance

  1. mutations affecting cell surface can affect entry of drug
    • prevents entry of drug into cell
  2. receptor normally used by drug altered- no binding.
    • example: mutations can affect drug target in cell (e.g. slight change in ribosomal RNA can change affinity of ribosomes for erythromycin)
  3. bacteria or plasmids can produce enzymes which inactivate drug; e.g. pencillinases hydrolyze ß-lactam ring.
    • Plasmids = small, circular DNA elements that reside in bacterial cells, duplicate separately from bacterial chromosome.
    • Some plasmids carry genes for antibiotic resistance (enzymes that degrade antibiotic). Called R-plasmids. Have been found for most classes of antibiotics.
    • When antibiotics are in use, most bacteria are killed. If R-plasmid exists, can be transferred to other cells, resistance spreads through population. Result: new population is resistant to drug.
    • Note: possible for a single plasmid to carry multiple drug resistance genes, spread all of these as a single unit!
  4. plasmid encoded drug pump
    • production of protein "pumps" to pump drug out of cell

Ways to deal with antibiotic resistance

  1. higher dose, different antibiotic, more than one drug simultaneously
  2. also restraint by physicians and control (no over the counter use)
  3. CORRECT use of drug. Most people take drugs improperly, miss doses, allow conditions that favor selection of drug resistant mutants.

A. Non-specific Defenses

Tissue barriers

Chemical barriers

Phagocytes

Inflammation


Take a Self-Quiz on Ch. 33 material
Take a Self-Quiz on Ch. 29 material
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