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.

超广谱头孢菌素 (ESC) 是抗菌药物，用于治疗严重的细菌感染，例如由肠杆菌科引起的感染，肠杆菌科是革兰氏阴性菌的一个大家族，其中包括许多常见的病原体，包括沙门氏菌、大肠杆菌、鼠疫耶尔森菌（致病菌）鼠疫）、克雷伯氏菌和志贺氏菌（引起细菌性痢疾）。肠杆菌科细菌对ESCs的耐药性是全球公共卫生面临的重大挑战。国际上几乎每个生态位和生物区室（包括动物和人类）都存在 ESC 耐药性，这使其成为研究抗菌素耐药性 (AMR) 传播的理想目标。该项目打算使用高分辨率全基因组、转录组和蛋白质数据以及进化和实验方法来评估由肠杆菌科物种、宿主物种/来源（人类、狗、牛、猪、鸡肉、肉制品）和地理（欧洲：德国和法国，北美：加拿大）。这些相似之处将成为使用全基因组测序识别和进一步关注细菌亚型及其能够跨区室传播的移动遗传元件（例如质粒）的基础。结合分析方法将可以评估隔室之间传播的方向性。这些分析将得到一系列关于 ESC 抗性质粒在两种动物模型（鸡和牛）中的传播以及 ESC 抗性质粒对其细菌宿主的影响的现场实验的补充。这些实验将有助于确定动物和人类之间的主要传播途径以及控制ESC耐药性的潜在新干预目标。为本项目组建的团队由经验丰富的研究人员组成，他们拥有广泛的专业知识，非常适合在 One Health 背景下成功完成抗菌素耐药性研究。

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.