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dc.contributor.authorGuo, Yingyi
dc.contributor.authorLiu, Ningjing
dc.contributor.authorLin, Zhiwei
dc.contributor.authorBa, Xiaoliang
dc.contributor.authorZhuo, Chuyue
dc.contributor.authorLi, Feifeng
dc.contributor.authorWang, Jiong
dc.contributor.authorLi, Yitan
dc.contributor.authorYao, Likang
dc.contributor.authorLiu, Baomo
dc.contributor.authorXiao, Shunian
dc.contributor.authorJiang, Ying
dc.contributor.authorZhuo, Chao
dc.date.accessioned2021-12-17T00:31:16Z
dc.date.available2021-12-17T00:31:16Z
dc.date.issued2021-12
dc.identifier.issn2222-1751
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331572
dc.description.abstractCeftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify novel CAZ-AVI resistance mechanism, we generated 10 CAZ-AVI-resistant strains from 14 CAZ-AVI susceptible KPC-producing K. pneumoniae (KPC-Kp) strains through in vitro multipassage resistance selection using low concentrations of CAZ-AVI. Comparative genomic analysis for the original and derived mutants identified CAZ-AVI resistance-associated mutations in KPCs, PBP3 (encoded by ftsI), and LamB, an outer membrane maltoporin. CAZ-AVI susceptible KPC-Kp strains became resistant when complemented with mutated blaKPC genes. Complementation experiments also showed that a plasmid borne copy of wild-type lamB or ftsI gene reduced the MIC value of CAZ-AVI in the induced resistant strains. In addition, blaKPC expression level increased in four of the six CAZ-AVI-resistant strains without KPC mutations, indicating a probable association between increased blaKPC expression and increased resistance in these strains. In conclusion, we here identified a novel mechanism of CAZ-AVI resistance associated with mutations in porin LamB in KPC-Kp.
dc.format.mediumPrint
dc.publisherInforma UK Limited
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCeftazidime-avibactam
dc.subjectKPC
dc.subjectLamB
dc.subjectPBP3
dc.subjectexpression level of blaKPC
dc.titleMutations in porin LamB contribute to ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae.
dc.typeArticle
dc.publisher.departmentDepartment of Veterinary Medicine
dc.date.updated2021-12-16T11:51:46Z
prism.endingPage2051
prism.issueIdentifier1
prism.publicationDate2021
prism.publicationNameEmerg Microbes Infect
prism.startingPage2042
prism.volume10
dc.identifier.doi10.17863/CAM.79025
dcterms.dateAccepted2021-09-19
rioxxterms.versionofrecord10.1080/22221751.2021.1984182
rioxxterms.versionVoR
dc.contributor.orcidBa, Xiaoliang [0000-0002-3882-3585]
dc.identifier.eissn2222-1751
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-11-02
cam.depositDate2021-12-16
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International