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

抗菌素耐药性（AMR）的发生在世界范围内迅速增加，包括在健康的人和动物种群中发现的细菌中。最近关于粘菌素耐药性的报告，可能与粘菌素在农业中的使用有关，这进一步引起了人们对由于抗菌素耐药性而变得无法治疗的感染的担忧。人类和动物的共生菌群是抗菌素耐药性基因的储存库，而作为健康菌群一部分的大肠杆菌可携带多种抗菌素耐药性决定因子。在大肠杆菌内的抗微生物药物耐药性传播似乎主要是由某些遗传类型的有机体。然而，这些疾病在多大程度上局限于某些宿主物种（动物/人类等）尚不清楚。这种宿主限制可能是耐药大肠杆菌在不同宿主之间（如动物和人类宿主之间）传播可能性的重要决定因素。鉴定能够解开抗菌素耐药性不同传播模式的基因，对于更有针对性地设计预防和减少抗菌素耐药性传播的控制措施至关重要。本研究旨在鉴定大肠杆菌宿主限制基因及其与AMR传播和发生的潜在关联。我们建议利用来自欧洲和越南不同地理区域的人类、动物和环境来源的大量大肠杆菌分离物的全基因组测序，实验模型来研究宿主限制决定因素在传播和细菌适应性中的作用，并建立数学模型。该研究旨在进行风险评估，估计不同传播途径的贡献，并预测控制抗生素耐药性的效果。该联盟在开展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，他们在人类和动物卫生领域工作，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.