Genomic approach to transmission and compartmentalization of extended-spectrum cephalosporin resistance in Enterobacteriaceae from animals and humans

动物和人类肠杆菌科细菌中广谱头孢菌素耐药性的传播和区划的基因组方法

• 批准号: MR/R000948/1
• 负责人: James Wood
• 金额: $ 38.8万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=MR%2FR000948%2F1
• 关键词: Genomic; approach; transmission; compartmentalization; extended

Extended-spectrum cephalosporins (ESCs) are antimicrobial drugs which are used to treat serious bacterial infections such as those caused by Enterobacteriaceae, a large family of Gram-negative bacteria that includes many familiar pathogens, including Salmonella, Escherichia coli, Yersinia pestis (the cause of plague), Klebsiella and Shigella (the cause of bacterial dysentery). Resistance to ESCs in Enterobacteriaceae is a major challenge for public health worldwide. The international presence of ESC resistance in almost every ecological niche and biological compartment, including both animals and humans, makes it an ideal target to study the spread of antimicrobial resistance (AMR). This project intends to use high resolution whole genome, transcriptome, and protein data along with evolutionary and experimental approaches to assess the similarities between a variety of ecological niches and biological compartments formed by Enterobacteriaceae species, host species/source (humans, dogs, cattle, swine, chicken, meat products) and geography (Europe: Germany and France, and North America: Canada). These similarities will serve as a basis to identify and focus further on bacterial subtypes and their mobile genetic elements (such as plasmids) able to spread across compartments, using whole genome sequencing. A combination of analytical approaches will allow an assessment of the directionality of transmission between compartments. These analyses will be complemented by series of field experiments on the transmission of ESC resistance plasmids in two animal models (chicken and cattle), and on the effects of ESC resistance plasmids on their bacterial hosts. These experiments will help to identify major transmission pathways between animals and humans and potential new intervention targets for the control of ESC resistance. The team assembled for this project consists of experienced researchers with a wide spectrum of expertise ideal for the successful completion of a study of antimicrobial resistance in the context of One Health.

Extended-spectrum cephalosporins (ESCs) are antimicrobial drugs which are used to treat serious bacterial infections such as those caused by Enterobacteriaceae, a large family of Gram-negative bacteria that includes many familiar pathogens, including Salmonella, Escherichia coli, Yersinia pestis (the cause of plague), Klebsiella and Shigella (the cause of bacterial痢疾）。肠杆菌科中对ESC的抵抗是全球公共卫生的主要挑战。包括动物和人类在内的几乎每个生态群体和生物隔室中ESC抗性的国际存在，使其成为研究抗菌耐药性传播（AMR）的理想目标。该项目旨在使用高分辨率的整个基因组，转录组和蛋白质数据，以及进化和实验方法，以评估由肠杆菌种类，寄主物种/来源（人类，狗，狗，狗，牛，牛，猪，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉，鸡肉）和地理（欧洲和弗朗西斯和诺斯市）形成的各种生态壁ches与生物隔室之间的相似性。这些相似性将作为基础，以进一步识别和关注细菌亚型及其移动遗传元素（例如质粒），能够使用整个基因组测序能够在隔室中散布。分析方法的组合将允许评估隔室之间传输的方向性。这些分析将通过两种动物模型（鸡肉和牛）以及ESC耐药性质粒对细菌宿主的影响的一系列现场实验进行补充。这些实验将有助于确定动物与人之间的主要传播途径，并潜在的新干预目标以控制ESC耐药性。为该项目组成的团队由经验丰富的研究人员组成，这些研究人员具有广泛的专业知识，非常适合在一个健康状况下成功完成抗菌耐药性研究。

项目成果

Diversity of blaCTX-M-1-carrying plasmids recovered from Escherichia coli isolated from Canadian domestic animals.

• DOI: 10.1371/journal.pone.0264439
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Cormier AC;Chalmers G;Zamudio R;Mulvey MR;Mather AE;Boerlin P
• 通讯作者: Boerlin P

Dynamics of extended-spectrum cephalosporin resistance genes in Escherichia coli from Europe and North America.

• DOI: 10.1038/s41467-022-34970-7
• 发表时间: 2022-12-12
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Zamudio, Roxana;Boerlin, Patrick;Beyrouthy, Racha;Madec, Jean-Yves;Schwarz, Stefan;Mulvey, Michael R.;Zhanel, George G.;Cormier, Ashley;Chalmers, Gabhan;Bonnet, Richard;Haenni, Marisa;Eichhorn, Inga;Kaspar, Heike;Garcia-Fierro, Raquel;Wood, James L. N.;Mather, Alison E.
• 通讯作者: Mather, Alison E.