High-Level Resistance to Colistin Mediated by Various Mutations in the crrB Gene among Carbapenemase-Producing Klebsiella pneumoniae

Aurélie Jayol; Patrice Nordmann; Adrian Brink; Maria-Virginia Villegas; Véronique Dubois; Laurent Poirel

doi:10.1128/AAC.01423-17

High-Level Resistance to Colistin Mediated by Various Mutations in the crrB Gene among Carbapenemase-Producing Klebsiella pneumoniae

Antimicrob Agents Chemother. 2017 Oct 24;61(11):e01423-17. doi: 10.1128/AAC.01423-17. Print 2017 Nov.

Authors

Aurélie Jayol^{1

2

3

4

5}, Patrice Nordmann^{1

2

3

6}, Adrian Brink⁷, Maria-Virginia Villegas⁸, Véronique Dubois^{4

5}, Laurent Poirel^{9

2

3}

Affiliations

¹ Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
² INSERM European Unit (LEA Paris, IAME, France), University of Fribourg, Fribourg, Switzerland.
³ National Reference Center for Emerging Antibiotic Resistance, University of Fribourg, Fribourg, Switzerland.
⁴ Laboratory of Bacteriology, Bordeaux University Hospital, Bordeaux, France.
⁵ CNRS UMR5234, University of Bordeaux, Bordeaux, France.
⁶ University of Lausanne and University Hospital Center, Lausanne, Switzerland.
⁷ Department of Clinical Microbiology, Ampath National Laboratory Services, Milpark Hospital, Johannesburg, South Africa.
⁸ International Center for Medical Research and Training, CIDEIM, Cali, Colombia.
⁹ Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland laurent.poirel@unifr.ch.

Abstract

Mutations in crrAB genes encoding a two-component regulator involved in modifications of lipopolysaccharide were searched for among a collection of colistin-resistant Klebsiella pneumoniae isolates. Four isolates, respectively, producing carbapenemases NDM-1, OXA-181, or KPC-2 showed mutated CrrB proteins compared with those in wild-type strains. Complementation assays with a wild-type CrrB protein restored the susceptibility to colistin in all cases, confirming the involvement of the identified substitutions in the resistance phenotype.

Keywords: CrrAB; Klebsiella pneumoniae; polymyxin; rapid polymyxin NP test; resistance mechanisms; susceptibility testing.

MeSH terms

Amino Acid Substitution
Anti-Bacterial Agents / pharmacology*
Bacterial Proteins / genetics*
Bacterial Proteins / metabolism
Colistin / pharmacology*
Drug Resistance, Bacterial / drug effects
Drug Resistance, Bacterial / genetics*
Gene Expression Regulation, Bacterial / drug effects
Genetic Complementation Test
Humans
Klebsiella pneumoniae / drug effects*
Klebsiella pneumoniae / genetics
Klebsiella pneumoniae / isolation & purification
Klebsiella pneumoniae / metabolism
Microbial Sensitivity Tests
Mutation
beta-Lactamases / genetics
beta-Lactamases / metabolism

Substances

Anti-Bacterial Agents
Bacterial Proteins
beta-Lactamases
beta-lactamase KPC-2, Klebsiella pneumoniae
beta-lactamase NDM-1
carbapenemase
Colistin