Investigating the Fitness Differences of Mobile Colistin Resistance Genes

抗生素耐药性危机是一个世界性的问题，也是当前的主要科学焦点之一。最近，在大肠杆菌中发现了通过mcr-1对粘菌素的移动耐药，粘菌素是对抗革兰氏阴性菌的最后一种抗生素之一，尽管该基因的表达给细菌带来了很大的适应成本。多个移动粘菌素耐药(MCR)基因变异体和同源物已经在全球范围内被鉴定出来。该项目旨在评估这些同系物和变种的健康成本，以确定这些成本是否正在减轻。发现的任何适应性变化都可能是抵抗力进化和/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类MCR基因的遗传进化。研究粘菌素带来的成本以及移动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，并影响我们未来如何使用粘菌素。BBSRC优先AREAT他的项目解决了涉及抗生素耐药性基因和细菌耐药性进化的主题。这里讨论的主题与BBSRC“生物科学促进健康”的研究主题密切相关，这里概述的研究涉及“抗击抗菌素耐药性”的优先领域，因为我们的目标是使用生物技术来了解粘菌素耐药性基因的进化和传播及其编码的蛋白质的结构和功能。

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.