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Strategy 3: Inactivation of antimicrobial agents via modification or degradation.

Another means by which bacteria preserve themselves is by destroying the active component of the antimicrobial agent.  A classic example is the hydrolytic deactivation of the beta-lactam ring in penicillins and cephalosporins by the bacterial enzyme called beta lactamase.  The inactivated penicilloic acid will then be ineffective in binding to PBPs (penicllin binding proteins), thereby protecting the process of cell wall synthesis. 

This strategy has also been observed in:

  • Enterobacteriaceae against chloramphenicol (acetylation)
  • Gram negative and Gram positive bacteria against aminoglycosides (phosphorylation, adenylation, and acetylation)

 

 

 

 

Trivia: first evidence of antimicrobial resistance

The first antibiotic resistance mechanism described was that of penicillinase.  Its presence and activity was first reported by Abraham and Chain in 1940 shortly after its discovery (Abraham, E. P. and E. Chain. 1940. An enzyme from bacteria able to destroy penicillin. Nature 146: 837)

Resistance Mechanisms Keeping Up

microscope_image.jpgLess than 10 years after the clinical introduction of penicillins, penicillin-resistant Staphylococcus aureus was observed in a majority of Gram-positive infections in people. The initial response by the pharmaceutical industry was to develop beta-lactam antibiotics that were unaffected by the specific beta-lactamases secreted by S. aureus.  However, as a result, bacterial strains producing beta-lactamases with different properties began to emerge, as well as those with other resistance mechanisms. This cycle of resistance counteracting resistance continues even today (Bush, 1988. Beta-Lactamase Inhibitors from Laboratory to Clinic. Clinical Microbiology Reviews. 1(1):109-123.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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