The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae
Top Cited Papers
- 3 September 2014
- journal article
- Published by Oxford University Press (OUP) in Journal of Antimicrobial Chemotherapy
- Vol. 70 (1), 75-80
- https://doi.org/10.1093/jac/dku323
Abstract
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.Keywords
This publication has 18 references indexed in Scilit:
- In Vivo Evolution to Colistin Resistance by PmrB Sensor Kinase Mutation in KPC-Producing Klebsiella pneumoniae Is Associated with Low-Dosage Colistin TreatmentAntimicrobial Agents and Chemotherapy, 2014
- In Vivo Emergence of Colistin Resistance in Klebsiella pneumoniae Producing KPC-Type Carbapenemases Mediated by Insertional Inactivation of the PhoQ/PhoP mgrB RegulatorAntimicrobial Agents and Chemotherapy, 2013
- Genomic analysis of the emergence and evolution of multidrug resistance during a Klebsiella pneumoniae outbreak including carbapenem and colistin resistanceJournal of Antimicrobial Chemotherapy, 2013
- Colistin: an update on the antibiotic of the 21st centuryExpert Review of Anti-infective Therapy, 2012
- Colistin: new lessons on an old antibioticClinical Microbiology & Infection, 2012
- Global Spread of Carbapenemase-producingEnterobacteriaceaeEmerging Infectious Diseases, 2011
- Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in Klebsiella pneumoniae CG43Journal of Biomedical Science, 2010
- Resistance to polymyxins: Mechanisms, frequency and treatment optionsDrug Resistance Updates, 2010
- The Pleiotropic Two-Component Regulatory System PhoP-PhoQJournal of Bacteriology, 2001
- Molecular Characterization of the PhoP-PhoQ Two-Component System in Escherichia coli K-12: Identification of Extracellular Mg 2+ -Responsive PromotersJournal of Bacteriology, 1999