Molecular epidemiology of antimicrobial resistance plasmids in bacteria from animals

动物细菌中抗菌素耐药性质粒的分子流行病学

• 批准号: RGPIN-2015-03962
• 负责人: Boerlin, Patrick
• 金额: $ 2.04万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=682589
• 关键词: Molecular; epidemiology; antimicrobial; resistance; plasmids

This proposal is part of our extended efforts to understand better the epidemiology of antimicrobial resistance (AMR) in bacteria from animals using molecular methods. The unique approach proposed is to focus on a geographically limited region (Ontario), but to look simultaneously at a broader group of bacteria (i.e. not only E. coli and Salmonella, but Enterobacteriaceae in general) than has traditionally been examined in the past. Based on results from more focused studies, the hypotheses I want to test are that AMR determinants do not flow equally from one ecological compartment to another, resulting in compartmentalization 1) at the bacterial species level, 2) at the animal host species level, and 3) at the commensal/pathogen levels. My fourth hypothesis is that the latter phenomenon can be partially explained by the linkage of AMR and virulence determinants on mobile genetic elements (plasmids) and that these linkages stabilize AMR determinants, thus partially explaining the higher prevalence of AMR in pathogens. To test these hypotheses, I will concentrate efforts on resistance to cephalosporins and fluoroquinolones, and compare the distribution of resistance determinants to these clinically critically important antimicrobials in commensals and pathogens from four farm and companion animal species. The distribution of these determinants among bacterial species, animal species, and commensal/pathogens will allow to test the compartmentalization hypothesis and to identify the main commonalities and bottlenecks in the diffusion of AMR determinants. The observed distribution will allow to select representative commensals and pathogens and to sequence their genomes in order to understand precisely the associations/linkages between AMR genes and between AMR and virulence determinants in the population under study. Finally, to test the last hypothesis, in vivo experiments will be conducted to assess the persistence of resistance and pathogens with linked and non-linked AMR and virulence determinants using wild type and genetically engineered E. coli strains. The expected results of this study will provide new and broader insights into AMR epidemiology at the complex interface of bacterial species, host species, and reservoir-pathogen interactions than has been provided by the past uncoordinated studies on AMR in bacterial from animals. The proposed work will form the basis for the training of one MSc, one PhD, and at least five undergraduate students.

该提案是我们使用分子方法更好地了解动物细菌抗菌素耐药性（AMR）流行病学的扩展努力的一部分。提出的独特方法是集中在地理上有限的区域（安大略），但同时着眼于更广泛的细菌群（即不仅是E。大肠杆菌和沙门氏菌，但一般肠杆菌科）比过去传统上检查。基于更有针对性的研究结果，我想检验的假设是，AMR决定因素从一个生态区室到另一个生态区室的流动并不相等，导致1）在细菌物种水平，2）在动物宿主物种水平，3）在细菌/病原体水平的划分。我的第四个假设是，后一种现象可以部分解释为AMR和移动的遗传元件（质粒）上的毒力决定簇的联系，这些联系稳定了AMR决定簇，从而部分解释了AMR在病原体中的较高流行率。为了检验这些假设，我将集中精力对头孢菌素类和氟喹诺酮类抗生素的耐药性，并比较耐药决定因素的分布，这些临床上非常重要的抗菌药物中的抗生素和病原体从四个农场和伴侣动物物种。这些决定因素在细菌种属、动物种属和共生/病原体中的分布将有助于检验区室化假设，并确定AMR决定因素扩散的主要共性和瓶颈。观察到的分布将允许选择代表性的细菌和病原体，并对其基因组进行测序，以准确了解研究人群中AMR基因之间以及AMR与毒力决定因子之间的关联/联系。最后，为了检验最后一个假设，将使用野生型和基因工程大肠杆菌进行体内实验，以评估耐药性和具有连锁和非连锁AMR和毒力决定因子的病原体的持久性。大肠杆菌菌株。本研究的预期结果将提供新的和更广泛的见解AMR流行病学在复杂的界面的细菌种属，宿主种属，和病原体-病原体相互作用比已经提供了过去的不协调的研究AMR的细菌从动物。拟议的工作将形成一个硕士，一个博士和至少五名本科生的培训基础。