Investigating the Fitness Differences of Mobile Colistin Resistance Genes

研究移动粘菌素抗性基因的适应性差异

• 批准号: 1945628
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1945628
• 关键词: Investigating; Fitness; Differences; Mobile; Colistin

The antibiotic resistance crisis is a worldwide problem and one of the major scientific focuses currently. Recently, plasmid mediated mobile resistance to colistin, one of the last-resort antibiotics against gram-negative bacteria, via mcr-1 has been discovered in E. coli although expression of this gene imposes a major fitness cost on bacteria. Multiple mobile colistin resistance (MCR) gene variants and homologs have since been identified globally. This project aims to assess the fitness costs of these homologs and variants in order to determine if these costs are being alleviated. Any fitness changes identified could be examples of resistance evolution and/or compensatory adaptation. If successful, this project could allow us to study genetic evolution of MCR-like genes in real-time. Studying the costs that colistin imposes and how mobile colistin resistance genes are evolving could provide insights on how to preserve the efficacy of this important antibiotic and impact how we use colistin in the future. BBSRC PRIORITY AREAThis project tackle topics involving antibiotic resistance genes and the evolution of resistance in bacteria. Topics discussed here strongly link to the BBSRC "Bioscience for Health" research topic and the research outlined here addresses the "Combatting antimicrobial resistance" priority area as we aim to use biological techniques to understand the evolution and spread of colistin resistance genes and the structure and function of the proteins they encode.

抗生素耐药性危机是一个世界性的问题，也是当前科学界关注的焦点之一。近年来，在大肠杆菌中发现了质粒介导的mcr-1对革兰阴性菌最后的抗生素之一黏菌素的移动的耐药性。尽管该基因的表达对细菌施加了主要的适应性成本。此后，在全球范围内发现了多种移动的粘菌素耐药（MCR）基因变体和同源物。该项目旨在评估这些同系物和变体的适应性成本，以确定这些成本是否正在减轻。确定的任何适应性变化都可能是抗性进化和/或补偿性适应的例子。如果成功，这个项目可以让我们实时研究MCR样基因的遗传进化。研究粘菌素的成本以及移动的粘菌素耐药基因是如何进化的，可以为如何保持这种重要抗生素的疗效提供见解，并影响我们未来使用粘菌素的方式。BBSRC优先领域这个项目涉及抗生素耐药基因和细菌耐药性的演变。这里讨论的主题与BBSRC“健康生物科学”研究主题密切相关，这里概述的研究涉及“对抗抗菌素耐药性”优先领域，因为我们的目标是使用生物技术来了解粘菌素耐药基因的进化和传播以及它们编码的蛋白质的结构和功能。