The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae

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dc.contributor.authorPoirel, Laurent
dc.contributor.authorJayol, Aurelie
dc.contributor.authorBontron, Severine
dc.contributor.authorVillegas, Maria-Virginia
dc.contributor.authorÖzdamar, Melda
dc.contributor.authorTürkoğlu, Salih
dc.contributor.authorNordmann, Patrice
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:57:19Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:57:19Z
dc.date.issued2015
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Ana Bilim Dalı
dc.descriptionWOS: 000350210800010
dc.descriptionPubMed ID: 25190723
dc.description.abstractObjectives: Alterations in the PhoPQ two-component regulatory system may be associated with colistin resistance in Klebsiella pneumoniae. MgrB is a small transmembrane protein produced upon activation of the PhoPQ signalling system, and acts as a negative regulator on this system. We investigated the role of the MgrB protein as a source of colistin resistance in a series of K. pneumoniae. Methods: Colistin-resistant K. pneumoniae isolates were recovered from hospitalized patients worldwide (France, Turkey, Colombia and South Africa). The mgrB gene was amplified and sequenced. A wild-type mgrB gene was cloned and the corresponding recombinant plasmid was used for complementation assays. Clonal diversity was evaluated by MLST and Diversilab analysis. Results: Of 47 colistin-resistant isolates, 12 were identified as having a mutated mgrB gene. Five clonally unrelated isolates had an mgrB gene truncated by an IS5-like IS, while one clone also harboured an insertional inactivation at the exact same position of the mgrB gene, but with ISKpn13. Another clone harboured an insertional inactivation due to ISKpn14 at another location of the mgrB gene. Two clonally related isolates harboured an IS (IS10R) in the promoter region of mgrB. Finally, three clonally unrelated isolates harboured substitutions leading to anticipated stop codon in the MgrB protein. Complementation assays with a wild-type MgrB protein restored full susceptibility to colistin for all colistin-resistant isolates identified with qualitative or quantitative MgrB modifications. Conclusion: The inactivation or down-regulation of the mgrB gene was shown to be a source of colistin resistance in K. pneumoniae. Interestingly, identical genetic events were identified among clonally unrelated isolates.
dc.description.sponsorshipINSERM, France; University of Fribourg, Switzerland; European Community (R-GNOSIS) [FP7/HEALTH-F3-2011-282512]; European Community (MAGIC-BULLET) [FP7/HEALTH-F3-2001-278232]en_US
dc.description.sponsorshipThis work was funded by the INSERM, France, by the University of Fribourg, Switzerland, and by grants from the European Community (R-GNOSIS, FP7/HEALTH-F3-2011-282512 and MAGIC-BULLET, FP7/HEALTH-F3-2001-278232).en_US
dc.identifier.citationPoirel, L., Jayol, A., Bontron, S., Villegas, M. V., Özdamar, M., Türkoğlu, S. ve Nordmann, P. (2015). The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae. Journal of Antimicrobial Chemotherapy, 70(1), 75-80. https://dx.doi.org/10.1093/jac/dku323
dc.identifier.doi10.1093/jac/dku323
dc.identifier.endpage80
dc.identifier.issn0305-7453
dc.identifier.issn1460-2091
dc.identifier.issue1
dc.identifier.scopusqualityQ1
dc.identifier.startpage75
dc.identifier.urihttps://dx.doi.org/10.1093/jac/dku323
dc.identifier.urihttps://hdl.handle.net/20.500.12511/2949
dc.identifier.volume70
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherOxford University Press
dc.relation.ispartofJournal of Antimicrobial Chemotherapyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGene Inactivation
dc.subjectPhoPQ Regulatory System
dc.subjectPolymyxin
dc.subjectKlebsiella Pneumoniae
dc.titleThe mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae
dc.typeArticle

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