Mechanisms of Resistance to beta lactams

Beta lactamases

Beta lactamases are one of the most effective mechanisms of resistance to beta-lactam antibiotics. 1 Beta-lactamases are bacterial enzymes that provide antibiotic resistance to beta-lactams by splitting the amide bond of the beta-lactam ring, thereby inactivating the antibiotic. 8 They are secreted into the periplasmic space in gram negative bacteria or into the surrounding medium by gram positive organisms.

Beta lactamase (bla) genes can be found on the bacteria’s chromosome, plasmids or transposons. 6,7 The presence of bla genes in mobile elements, such as plasmids and transposons, is important as they contribute to the spreading of resistance to various bacterial species. 6,7

The ability of a beta-lactamase to inactivate a beta-lactam agent depends on the following factors:

  • the speed at which the beta-lactam is hydrolyzed
  • the amount of beta-lactamase produced by the organism
  • the affinity of the beta-lactamase for the beta-lactam agent
  • the susceptibility of the target to the beta-lactam
  • the concentration of the beta-lactam in the periplasmic cell space. (8)

Beta-lactamases have been classified using many criteria. The two most used classification systems are the Ambler molecular classification system, which divides the enzymes based on similarity in amino acid structure into Classes A-D; and the Bush-Jacoby-Medeiros (B-J-M),  which creates functional Groups 1 through 4 based on their substrate profile and susceptibility to beta-lactamase inhibitors. (5 -7,10)

It is beyond the scope of this article to review each group in detail and the reader is directed to the literature for more information on this topic. 

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