Journal
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume 51, Issue 6, Pages 822-828Publisher
ELSEVIER
DOI: 10.1016/j.ijantimicag.2018.01.004
Keywords
IS1294b; IncI2; pmrA; mcr-1; Fitness cost; ST359
Funding
- State's Key Project of Research and Development Plan [2017YFC1200200]
- National Natural Science Foundation of China [81702045, 81361138021, 81702040]
- Fundamental Research Funds for the Central Universities [2016FZA7008]
- National Basic Research Program of China [2015CB554201]
- Key Research and Development Program of Zhejiang Province [2015C03032]
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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. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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