Heteroresistance to colistin in Klebsiella pneumoniae associated with alterations in the PhoPQ regulatory system.
A multidrug-resistant Klebsiella pneumoniae isolate exhibiting heteroresistance to colistin was investigated. The colistin-resistant subpopulation harbored a single amino acid change (Asp191Tyr) in protein PhoP, which is part of the PhoPQ two-component system that activates pmrHFIJKLM expression responsible for l-aminoarabinose synthesis and polymyxin resistance. Complementation assays with a wild-type phoP gene restored full susceptibility to colistin. Then, analysis of the colistin-susceptible subpopulation showed a partial deletion (25 bp) in the phoP gene compared to that in the colistin-resistant subpopulation. That deletion disrupted the reading frame of phoP, leading to a longer and inactive protein (255 versus 223 amino acids long). This is the first report showing the involvement of mutation(s) in PhoP in colistin resistance. Furthermore, this is the first study to decipher the mechanisms leading to colistin heteroresistance in K. pneumoniae.
Medical and Molecular Microbiology "Emerging Antibiotic Resistance" Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
Aurélie
A
Jayol
Medical and Molecular Microbiology "Emerging Antibiotic Resistance" Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland HFR-Hôpital Cantonal de Fribourg, Fribourg, Switzerland.
Patrice
P
Nordmann
Department of Clinical Microbiology, Ampath National Laboratory Services, Milpark Hospital, Johannesburg, South Africa.
Adrian
A
Brink
Medical and Molecular Microbiology "Emerging Antibiotic Resistance" Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland laurent.poirel@unifr.ch.
Laurent
L
Poirel
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003091:Colistin