The increasing prevalence of beta-lactamases among bacterial pathogens poses a public health challenge as antibiotics decline in efficacy. CMY-2, a plasmid-mediated class C beta-lactamase, confers resistance to cephamycins and broad-spectrum cephalosporins despite the presence of beta-lactamase inhibitors, such as tazobactam or clavulanic acid. Mutations to the completely conserved Asn152 in class C enzymes causes substrate selectivity switching and suggests a way in which these enzymes can acquire extended spectrum activity. The N152S mutant of CMY-2 was shown to exhibit selectivity switching for several substrates and inhibitors, acquiring increased resistance toward several new non-beta-lactam inhibitors and cefoxitin, at the expense of increased susceptibility to tazobactam. The structure of the N152S mutant of CMY-2 was determined using X-ray crystallography. Analysis of the N152S structure provides insight into the role Asn152 may play in the development of extended spectrum resistance.

Exploring the role of Asn152 in altering the resistance spectrum of the class C beta-lactamase CMY-2

243rd National Meeting (2012)

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