Co-existence of mcr-1 and blaCTX-M from porcine-derived Escherichia coli isolated in China and selection of mcr-1 under cephalosporins pressure.

IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES
Zixian Wang, Jingyi Guo, Gejin Lu, Jie Jing, Shiwen Sun, Yang Sun, Xue Ji, Bowen Jiang, Bing Liang, Chuanfang Zhao, Lin Zheng, Lingwei Zhu, Xuejun Guo
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引用次数: 0

Abstract

Objectives: The usage of cephalosporins (CEFs) and co-existence of extended-spectrum β-lactamase (ESBL) gene blaCTX-M in the same host may promote the prevalence of colistin (CST) resistance gene mcr-1. This study aims to investigate the underlying mechanisms how the mcr-1 and blaCTX-M demonstrate significant co-occurrence in Escherichia coli (E. coli).

Methods: Conjugation assays were performed on 22 porcine-derived mcr-1-positive and blaCTX-M-positive E. coli (MCRPEC::blaCTX-M+) isolates from China to assess co-transfer potential. Whole genome sequencing characterized the genetic localization and context of mcr-1 and blaCTX-M. Fitness cost and genetic stability were evaluated through growth curve and anti-microbial resistance (AMR) gene stability rates measurement. Additionally, we examined mcr-1 selection during blaCTX-M co-existence under CEFs pressure by monitoring fitness and stability variations in mcr-1.

Results: Successful co-transfer of mcr-1 and blaCTX-M occurred in 36% (8/22) of isolates, demonstrating co-transfer efficiency ranging from 1.3×10-5 to 1.5×10-3. Predominant plasmid combinations facilitating co-transfer were IncI2(mcr-1) + IncI1(blaCTX-M) combination. Notably, we report the first identification of blaCTX-M-positive E. coli (CTX-M-EC) carrying dual mcr-1 copies on plasmids. mcr-1 and blaCTX-M did not exhibit fitness costs in 63% (5/8) of transconjugants, with 88% (7/8) maintaining over 70% stable rate in 10 days. CEFs pressure enhanced both fitness and stability of mcr-1 in blaCTX-M co-harboring transconjugants.

Conclusions: The observed high co-transfer efficiency, high stability rates, and low fitness costs of mcr-1 and blaCTX-M across distinct plasmid types and the mcr-1 selection driven by CEFs support the co-existence of mcr-1 and blaCTX-M in E. coli hosts. Our findings support a suggestion that an urgent need for coordinated antibiotic stewardship targeting both drug classes to curb multidrug-resistant bacteria spread.

猪源性大肠杆菌mcr-1与blaCTX-M的共存及头孢菌素压力下mcr-1的选择
目的:头孢菌素(CEFs)的使用和广谱β-内酰胺酶(ESBL)基因blaCTX-M在同一宿主体内共存可能促进粘菌素(CST)耐药基因mcr-1的流行。本研究旨在探讨mcr-1和blaCTX-M在大肠杆菌中显著共存的潜在机制。方法:对22株猪源性mcr-1阳性和blaCTX-M阳性大肠杆菌(MCRPEC::blaCTX-M+)进行偶联试验,评估共转移潜力。全基因组测序鉴定了mcr-1和blaCTX-M的遗传定位和背景。通过生长曲线和抗菌素耐药性(AMR)基因稳定率的测定来评价适应度成本和遗传稳定性。此外,我们通过监测mcr-1的适应性和稳定性变化,研究了CEFs压力下blaCTX-M共存期间mcr-1的选择。结果:mcr-1与blaCTX-M共转移成功率为36%(8/22),共转移效率为1.3×10-5 ~ 1.5×10-3。促进共转移的主要质粒组合是IncI2(mcr-1) + IncI1(blaCTX-M)组合。值得注意的是,我们报告了首次鉴定的blactx - m阳性大肠杆菌(CTX-M-EC)在质粒上携带双mcr-1拷贝。63%(5/8)的转共轭体mcr-1和blaCTX-M不表现出适应成本,88%(7/8)的转共轭体在10天内保持70%以上的稳定率。CEFs压力增强了blaCTX-M共载转共轭子中mcr-1的适应性和稳定性。结论:观察到mcr-1和blaCTX-M在不同质粒类型间的高共转移效率、高稳定性和低适应成本,以及CEFs驱动的mcr-1选择支持mcr-1和blaCTX-M在大肠杆菌宿主中共存。我们的研究结果支持了一项建议,即迫切需要针对这两种药物进行协调的抗生素管理,以遏制多重耐药细菌的传播。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of global antimicrobial resistance
Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY
CiteScore
8.70
自引率
2.20%
发文量
285
审稿时长
34 weeks
期刊介绍: The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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