The impact of Host restriction of Escherichia coli on Transmission dynamics and spread of antimicrobial Resistance

抗菌素耐药性（AMR）的发生在全球范围内迅速增加，包括在健康人类和动物群体中发现的细菌。最近关于粘菌素耐药性的报告，可能与农业中粘菌素的使用有关，进一步引起了人们对由于AMR而无法治疗的感染的担忧。人类和动物的肠道植物群是AMR基因的储存库，而大肠杆菌作为健康微植物群的一部分，可以携带多种AMR决定簇。耐药性在大肠杆菌中的传播。大肠杆菌似乎是由某些遗传类型的生物体主导的。然而，在何种程度上这些仅限于某些宿主物种（动物/人类等）。不明这种宿主限制可能是耐药大肠杆菌传播可能性的重要决定因素。大肠杆菌之间的不同水库，如动物和人类宿主。鉴定允许不同AMR传播模式解开的基因对于更有针对性的控制设计以预防和减少AMR传播至关重要。本研究的目的是鉴定大肠杆菌的宿主限制基因。大肠杆菌的耐药性及其与AMR传播和发生的潜在关系。我们建议利用全基因组测序的一个大集合的E。从欧洲和越南不同地理区域的人类、动物和环境来源分离的大肠杆菌，研究宿主限制性决定因素在传播和细菌适应性中作用的实验模型，以及数学建模。该研究旨在进行风险评估，估计不同传播途径的贡献，并预测控制措施对AMR的影响。该联盟在执行这项研究方面具有独特的地位，因为它由微生物学和抗菌素耐药性领域的专家组成，他们在人类和动物健康领域工作，并代表高度互补的学科。

The occurrence of antimicrobial resistance (AMR) is rapidly increasing worldwide, including in bacteria found in healthy human and animal populations. The recent reports of colistin resistance, potentially associated with colistin usage in agriculture, further raise fears of infections that have become untreatable due to AMR. The commensal flora of humans and animals is a reservoir of AMR genes and Escherichia coli which is part of the healthy micro-flora can carry multiple AMR determinants. Antimicrobial resistance transmission within E. coli appears to be dominated by certain genetic types of the organism. However, to what extent these are restricted to certain host species (animals/humans etc.) is unknown. Such host restriction may be an important determinant of the likelihood of transmission of resistant E. coli between different reservoirs, such as between animal and human hosts. The identification of genes that allow disentanglement of the different modes of AMR transmission is crucial for a more targeted design of controls to prevent and reduce transmission of AMR. The proposed research aims to identify genes of host restriction of E. coli and their potential association with AMR transmission and occurrence. We propose to utilise whole genome sequencing of a large collection of E. coli isolates from human, animal and environmental sources in different geographic areas across Europe and in Vietnam, experimental models to study the role of host restriction determinants in transmission and bacterial fitness, and mathematical modelling. The research aims to produce a risk-assessment, estimating the contribution of different transmission routes and predicting the effect of controls on AMR. The consortium is uniquely placed to perform this research as it consists of experts in the field of microbiology and antimicrobial resistance, who work in human and animal health domains, and represent highly complementary disciplines.