Resistance to aztreonam-avibactam due to a mutation of SHV-12 in Enterobacter.

ABSTRACT: Aztreonam-avibactam is an important option against Enterobacterales producing metallo-β-lactamases (MBLs). We obtained an aztreonam-avibactam-resistant mutant of an MBL-producing Enterobacter mori strain by induced mutagenesis. Genome sequencing revealed an Arg244Gly (Ambler position) substitution of SHV-12 β-lactamase in the mutant. Cloning and susceptibility testing verified that the SHV-12 Arg244Gly substitution led to significantly reduced susceptibility to aztreonam-avibactam (MIC, from 0.5/4 to 4/4 mg/L) but with the loss of resistance to cephalosporins as tradeoff. Arg244 of SHV involves in the binding of avibactam by forming an arginine-mediated salt bridge and is a critical residue to interact with β-lactams. Molecular modeling analysis demonstrated that the Arg244Gly substitution

SUBMITTER: Wu S 

PROVIDER: S-EPMC10294450 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature