[Enzymatic resistance to imipenem in gram-negative bacilli: NMC-A, an original carbapenemase]

Abstract

Carbapenems such as imipenem are beta-lactam antibiotics usually stable to the hydrolytic activity of beta-lactamases. Nevertheless, resistance to imipenem by production of carbapenemases has been described in few species of Gram negative bacilli. This mechanism of resistance remains exceptional in Enterobacteriaceae. These carbapenemases are principally metallo-enzymes that possess a zinc ion in their active site. Enterobacter cloacae strain NOR-1, is resistant to imipenem by production of an inducible chromosomal beta-lactamase which is not a metallo-enzyme but an Ambler class A beta-lactamase. This enzyme displays a strong hydrolytic activity against carbapenems but also against cephamycins which has never been previously observed for beta-lactamases of this class. These properties suggest that NMC-A possesses an original tridimensional structure of its active site allowing hydrolysis of molecules generally protected by the configuration of their lateral chain. Crystallographic study of this enzyme will permit to understand its mechanism of action and serve the development of new beta-lactams stable to b-lactamase hydrolytic activity.