VIM-2 deep mutational scanning

Metallo-beta-lactamases (MBLs) degrade a broad spectrum of beta-lactam antibiotics, and are a major disseminating source for multidrug resistant bacteria. Despite many biochemical studies in diverse MBLs, molecular understanding of the roles of residues in the enzyme's stability and function, and especially substrate specificity, is lacking. Here, we employ deep mutational scanning (DMS) to generate comprehensive single amino acid variant data on VIM-2 by measuring the effect of thousands of VIM-2 mutants on the degradation of three representative classes of beta-lactams (ampicillin, cefotaxime, and meropenem) and at two different temperatures (25C and 37C).