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

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...

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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/
http://psasir.upm.edu.my/id/eprint/86868/1/Mutation%20of%20kvrA%20causes.pdf
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author Dulyayangkul, Punyawee
Wan Ahmad Kamil, Wan Nur Ismah
Douglas, Edward J. A.
Avison, Matthew B.
author_facet Dulyayangkul, Punyawee
Wan Ahmad Kamil, Wan Nur Ismah
Douglas, Edward J. A.
Avison, Matthew B.
author_sort Dulyayangkul, Punyawee
building UPM Institutional Repository
collection Online Access
description 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.
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spelling upm-868682021-12-29T04:14:54Z http://psasir.upm.edu.my/id/eprint/86868/ Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae Dulyayangkul, Punyawee Wan Ahmad Kamil, Wan Nur Ismah Douglas, Edward J. A. Avison, Matthew B. 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. American Society for Microbiology 2020 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/86868/1/Mutation%20of%20kvrA%20causes.pdf Dulyayangkul, Punyawee and Wan Ahmad Kamil, Wan Nur Ismah and Douglas, Edward J. A. and Avison, Matthew B. (2020) Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy, 64 (7). pp. 1-8. ISSN 0066-4804; ESSN: 1098-6596 https://journals.asm.org/doi/10.1128/AAC.02208-19 10.1128/AAC.02208-19
spellingShingle Dulyayangkul, Punyawee
Wan Ahmad Kamil, Wan Nur Ismah
Douglas, Edward J. A.
Avison, Matthew B.
Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae
title Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae
title_full Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae
title_fullStr Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae
title_full_unstemmed Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae
title_short Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae
title_sort mutation of kvra causes ompk35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in kpc-producing klebsiella pneumoniae
url http://psasir.upm.edu.my/id/eprint/86868/
http://psasir.upm.edu.my/id/eprint/86868/
http://psasir.upm.edu.my/id/eprint/86868/
http://psasir.upm.edu.my/id/eprint/86868/1/Mutation%20of%20kvrA%20causes.pdf