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; Ed 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, Ed J A Douglas, Matthew B Avison

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

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
DOIs	https://doi.org/10.1128/AAC.02208-19
Publication status	Accepted/In press - 9 Apr 2020

Access to Document

10.1128/AAC.02208-19

Embargoed Document

Full-text PDF (author accepted manuscript)
Accepted author manuscript, 265 KB
Embargo ends: 1/01/99
Request copy

Fingerprint Dive into the research topics of 'Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae'. Together they form a unique fingerprint.

Cite this

Dulyayangkul, P., Wan Ahmad Kamil, W. N. I., Douglas, E. J. A., & Avison, M. B. (Accepted/In press). Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/AAC.02208-19

@article{f4215f9862a44daf8923ce1043e84117,

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, {Ed J A} and Avison, {Matthew B}",

year = "2020",

month = apr,

day = "9",

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

language = "English",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

}

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, Ed J A

AU - Avison, Matthew B

PY - 2020/4/9

Y1 - 2020/4/9

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 -