Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae

Abstract

<jats:title>Abstract</jats:title><jats:p>Meropenem/vaborbactam resistance in <jats:italic>Klebsiella pneumoniae</jats:italic> is associated with loss of function mutations in the OmpK36 porin. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in <jats:italic>K. pneumoniae</jats:italic>. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor that controls capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing <jats:italic>K. pneumoniae</jats:italic> clinical isolate.</jats:p>