Mcr-1 facilitated selection of high-level colistin-resistant mutants in Escherichia coli

Abstract

ObjectivesThe mcr-1 gene is the first reported plasmid-mediated colistin resistance gene. It has caused worldwide concern about the colistin resistance in Gram-negative bacteria. The aim of this research was to study the impact of mcr-1 on the selection of high-level colistin resistance (HLCR) mutations in Escherichia coli and Klebsiella pneumoniae. MethodsWe detected the HLCR mutation rates of Enterobacteriaceae strains (K. pneumoniae XH209, KP10, and E. coli Q3, ATCC 25922) and their transformants harbouring the mcr-1 gene. Further analysis of the HLCR mutants was conducted by sequencing, plasmid elimination experiment, and real-time quantitative PCR. ResultsFor XH209, mean mutation rate of XH209-pMCR was 1.7 (95% confidence interval (CI) 0.76–2.54) × 10−8, while XH209 and XH209-pCR2.1 showed mutation rates of 2.0 (95% CI, 1.32–2.67) × 10−8 and 2.3 (95% CI 1.47–3.13) × 10−8. For KP10 and its derived strains KP10-pCR2.1, KP10-pMCR, the mutation rates were 3.5 (95% CI 0.77–6.13) × 10−8, 4.8 (95% CI 0.69–8.94) × 10−8 and 4.2 (95% CI 0.95–7.54) × 10−8 respectively. The mutation rates of E. coli strains Q3-pMCR and ATCC25922-pMCR were 3.4 (95% CI 0.19–7.47) × 10−8 and 1.54 (95% CI 0.27–2.8) × 10−9, which were significantly higher than their corresponding non-mcr-1-carrying strains (p < 0.05). ConclusionsBeside the knowledge that mcr-1 mediates low-level colistin resistance, this gene also facilitates selection of HLCR mutants in E. coli, but does not affect K. pneumoniae.