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Int J Antimicrob Agents. 2018 Jun;51(6):822-828. doi: 10.1016/j.ijantimicag.2018.01.004. Epub 2018 Jan 12.

Silent transmission of an IS1294b-deactivated mcr-1 gene with inducible colistin resistance.

Author information

1
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Medicine School, Zhejiang University, Hangzhou 310003, China; Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
2
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Medicine School, Zhejiang University, Hangzhou 310003, China.
3
Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
4
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Medicine School, Zhejiang University, Hangzhou 310003, China. Electronic address: xiaoyonghong@zju.edu.cn.

Abstract

Global dissemination of the mobile colistin resistance mcr-1 is of particular concern as colistin is one of the last-resort antibiotics for the treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria. In this study, an inactive form of mcr-1 in a fluoroquinolone-resistant and colistin-susceptible uropathogenic Escherichia coli isolate (ECO3347) was characterised. The mcr-1 gene was deactivated by insertion of a 1.7-kb IS1294b element flanked by two tetramers (GTTC) and located on a 62-kb pHNSHP45-like plasmid (p3347-mcr-1). Single-step and multistep selections were used to induce colistin resistance in vitro in ECO3347. ECO3347 acquired colistin resistance (MIC = 16-32 mg/L) only after a serial passage selection with increasing concentrations of colistin (2-8 mg/L). Deactivated mcr-1 was re-activated by loss of IS1294b without any remnants in most colistin-resistant mutants. In addition, a novel amino acid variant (Leu105Pro) in the CheY homologous receiver domain of PmrA was detected in one colistin-resistant mutant. Plasmid p3347-mcr-1+ carrying the re-activated mcr-1 gene is transferrable to E. coli J53 recipient with a high conjugation rate (ca. 10-1 cells per recipient cell). Transconjugants showed an identical growth status to J53, suggesting lack of a fitness cost after acquiring p3347-mcr-1+. These results highlight that the disrupted mcr-1 gene has the potential for wide silent dissemination with the help of pHNSHP45-like epidemic plasmids. Inducible colistin resistance may likely compromise the success of clinical treatment and infection control. Continuous monitoring of mcr-1 is imperative for understanding and tackling its dissemination in different forms.

KEYWORDS:

Fitness cost; IS1294b; IncI2; ST359; mcr-1; pmrA

[Indexed for MEDLINE]

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