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

• Main Authors: Dulyayangkul, Punyawee, Wan Ahmad Kamil, Wan Nur Ismah, Douglas, Edward J. A., Avison, Matthew B.
• Format: Article
• Language: English
• Published: American Society for Microbiology 2020
• Online Access: http://psasir.upm.edu.my/id/eprint/86868/1/Mutation%20of%20kvrA%20causes.pdf; http://psasir.upm.edu.my/id/eprint/86868/; https://journals.asm.org/doi/10.1128/AAC.02208-19

Meropenem-vaborbactam resistance in Klebsiella pneumoniae isolates is associated with loss-of-function mutations in the OmpK35 and OmpK36 porins. We identify two previously unknown loss-of-function mutations that confer cefuroxime resistance in K. pneumoniae isolates. 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 K. pneumoniae isolate.