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

Poirel, Laurent; Jayol, Aurélie; Bontron, Séverine; Villegas, Maria-Virginia; Ozdamar, Melda; Türkoglu, Salih; Nordmann, Patrice

doi:10.1093/jac/dku323

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Journal article

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

Poirel, Laurent Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - INSERM U914, South-Paris Medical School, K.-Bicêtre, Paris, France
Jayol, Aurélie INSERM U914, South-Paris Medical School, K.-Bicêtre, Paris, France
Bontron, Séverine Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
Villegas, Maria-Virginia International Center for Medical Research and Training, CIDEIM, Cali, Colombia
Ozdamar, Melda Medical Microbiology Department, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
Türkoglu, Salih Medical Microbiology Department, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
Nordmann, Patrice Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - INSERM U914, South-Paris Medical School, K.-Bicêtre, Paris, France - Hôpital Cantonal de Fribourg, Switzerland

03.09.2014

Published in:

Journal of Antimicrobial Chemotherapy. - 2015, vol. 70, no. 1, p. 75-80

English Objectives 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.

Faculty

Faculté des sciences et de médecine

Department

Médecine 3ème année

Language