The carbapenems represent a last line of defence class of �- lactam antibiotics that, until recently, were unaffected by clinically significant �-lactamases that inactivate all other classes of �- lactams.  Classes A, C and D �-lactamases rely on a nucleophilic serine hydroxyl group whereas Class B enzymes employ zinc ions for catalysis.  Class A, B and D carbapenemases are now encountered commonly in hospitals. Mechanism-based inhibitors for the Class A �-lactamases, discovered in the 1980s, are much less effective against Class A and Class D carbapenemases and are totally ineffective against Class B enzymes.An interdisciplinary team funded by the Canadian Institutes for Health Research and the  Medical Research Council in the UK is seeking solutions to carbapenem resistance.  Progress in identifying compounds capable of inhibiting both the serine and the metallo-carbapenemases based on rational design as well as on natural product leads will be outlined.

Toward a universal β-lactamase inhibitor: A collaborative, interdisciplinary, Canada-UK team effort

245th National Meeting (2013)

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