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

mcr-1 facilitated selection of high-level colistin-resistant mutants in Escherichia coli
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mcr-1促进大肠杆菌中高水平粘菌素抗性突变体的选择

DOI:
10.1016/j.cmi.2018.12.014
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发表时间:
2019-04-01
影响因子:
14.2
通讯作者:
Yu, Y.
Yu, Y.
中科院分区:
医学1区
文献类型:
--
作者:
Zhang, H.;Zhao, D.;Yu, Y.

文献摘要

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目的:mcr-1基因是首次报道的质粒介导的粘菌素耐药基因。它引起了全世界对革兰氏阴性细菌中粘菌素耐药性的关注。本研究的目的是研究mcr-1对大肠杆菌和肺炎克雷伯菌高水平粘菌素耐药性(HLCR)突变选择的影响。方法:检测携带mcr-1基因的肠杆菌科菌株(肺炎克雷伯菌XH209、KP10和大肠杆菌Q3、ATCC 25922)及其转化体的HLCR突变率。通过测序、质粒消除实验和实时定量PCR对HLCR突变体进行进一步分析。结果:XH209的平均突变率为1.7(95%置信区间(CI) 0.76 ~ 2.54) × 10(-8), XH209和XH209- pcr2.1的平均突变率分别为2.0 (95% CI 1.32 ~ 2.67) × 10(-8)和2.3 (95% CI 1.47 ~ 3.13) × 10(-8)。KP10及其衍生菌株KP10- pcr2.1、KP10- pmcr的突变率分别为3.5 (95% CI 0.77 ~ 6.13) × 10(-8)、4.8 (95% CI 0.69 ~ 8.94) × 10(-8)和4.2 (95% CI 0.95 ~ 7.54) × 10(-8)。大肠杆菌Q3-pMCR和ATCC25922-pMCR的突变率分别为3.4 (95% CI 0.19-7.47) × 10(-8)和1.54 (95% CI 0.27-2.8) × 10(-9),显著高于其对应的非mcr-1携带菌株(p < 0.05)。结论:除了知道mcr-1介导低水平粘菌素耐药性外,该基因还促进了大肠杆菌中HLCR突变体的选择,但不影响肺炎克雷伯菌。(C) 2018年欧洲临床微生物学与传染病学会。Elsevier Ltd.出版。版权所有。
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) x 10(-8) , while XH209 and XH209-pCR2.1 showed mutation rates of 2.0 (95% CI, 1.32-2.67) x 10(-8) and 2.3 (95% CI 1.47-3.13) x 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) x 10(-8), 4.8 (95% CI 0.69-8.94) x 10(-8) and 4.2 (95% CI 0.95 - 7.54) x 10(-8) respectively. The mutation rates of E. coli strains Q3-pMCR and ATCC25922-pMCR were 3.4 (95% CI 0.19-7.47) x 10(-8) and 1.54 (95% CI 0.27-2.8) x 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. (C) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.