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Published on: August 22, 2017
mcr-1 facilitated selection of high-level colistin-resistant mutants in Escherichia coli
1Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China.
Objectives:
The 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.
Methods:
We 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.
Results:
For 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).
Conclusions:
Beside 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.
Insights
The mcr-1 gene, a cause of colistin resistance, was studied for its effect on high-level colistin resistance (HLCR) mutations. This gene facilitates HLCR mutant selection in Escherichia coli but not Klebsiella pneumoniae.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- The emergence of plasmid-mediated colistin resistance, primarily through the mcr-1 gene, poses a significant global health threat.
- Colistin is a critical last-resort antibiotic for treating multidrug-resistant Gram-negative bacterial infections.
Purpose of the Study:
- To investigate the influence of the mcr-1 gene on the selection of high-level colistin resistance (HLCR) mutations.
- To determine if mcr-1 impacts HLCR mutation rates in specific Gram-negative bacteria, Escherichia coli and Klebsiella pneumoniae.
Main Methods:
- Detection of HLCR mutation rates in Enterobacteriaceae strains (E. coli and K. pneumoniae) with and without the mcr-1 gene.
- Utilized sequencing, plasmid elimination experiments, and real-time quantitative PCR for detailed analysis of HLCR mutants.
Main Results:
- The mcr-1 gene significantly increased mutation rates for high-level colistin resistance in Escherichia coli strains.
- In contrast, the presence of the mcr-1 gene did not significantly affect the HLCR mutation rates in Klebsiella pneumoniae strains.
Conclusions:
- The mcr-1 gene not only confers low-level colistin resistance but also actively facilitates the selection of high-level colistin resistance mutants in E. coli.
- The mcr-1 gene's impact on HLCR selection differs between bacterial species, specifically not affecting K. pneumoniae.
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