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

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.

• Authors: Kai Zhou, Qixia Luo, Qin Wang, Chen Huang, Haifeng Lu, John W A Rossen, Yonghong Xiao, Lanjuan Li
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 51 Issue 6 Pg. 822-828 (Jun 2018) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 29339296 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• DNA Transposable Elements
• Escherichia coli Proteins
• MCR-1 protein, E coli
• pmrA protein, Bacteria
• Colistin

Topics

• Aged
• Anti-Bacterial Agents (pharmacology)
• Bacterial Proteins (genetics)
• Colistin (pharmacology)
• Conjugation, Genetic (genetics)
• DNA Transposable Elements (genetics)
• Drug Resistance, Bacterial (genetics)
• Escherichia coli (drug effects, genetics, isolation & purification)
• Escherichia coli Proteins (genetics)
• Female
• Gene Transfer, Horizontal (genetics)
• Humans