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

Punyawee Dulyayangkul; Wan Nur Ismah Wan Ahmad Kamil; Edward J A Douglas; Matthew B Avison

doi:10.1128/AAC.02208-19

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

Punyawee Dulyayangkul, Wan Nur Ismah Wan Ahmad Kamil, Edward J A Douglas, Matthew B Avison

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling 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.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Early online date	23 Jun 2020
DOIs	https://doi.org/10.1128/AAC.02208-19
Publication status	E-pub ahead of print - 23 Jun 2020

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

abstract = "Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling 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.",

author = "Punyawee Dulyayangkul and {Wan Ahmad Kamil}, {Wan Nur Ismah} and Douglas, {Edward J A} and Avison, {Matthew B}",

year = "2020",

month = jun,

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doi = "10.1128/AAC.02208-19",

language = "English",

journal = "Antimicrobial Agents and Chemotherapy",

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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.

In: Antimicrobial Agents and Chemotherapy, 23.06.2020.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae

AU - Dulyayangkul, Punyawee

AU - Wan Ahmad Kamil, Wan Nur Ismah

AU - Douglas, Edward J A

AU - Avison, Matthew B

PY - 2020/6/23

Y1 - 2020/6/23

N2 - Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling 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.

AB - Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling 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.

U2 - 10.1128/AAC.02208-19

DO - 10.1128/AAC.02208-19

M3 - Article (Academic Journal)

C2 - 32312773

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

ER -

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

Abstract

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