One Health Framework for Investigating Antimicrobial Resistant Enterobacterales Population Dynamics in Southwestern Virginia by Whole Genome Sequencing

项目摘要 抗生素耐药性是全球公共卫生的主要威胁。中心疾病 控制和预防已经确定了产超广谱β内酰胺酶 肠球菌（ESBL-E）是一种严重威胁公共卫生的微生物，这些微生物引起 人类和各种兽医物种（包括狗和猫）的临床感染。 因此，采取“一个健康”的方式来认识和打击至关重要 抗菌素耐药性此外，粪便携带相同菌株的ESBL-E。大肠杆菌已经被 被证明在同一个家庭中的人类和宠物之间共享。但 宠物和人感染ESBL-E临床分离株之间的关系 人口水平尚不清楚。这项研究的目的是：1）扩大弗吉尼亚理工大学的能力 动物实验室服务进行全基因组测序和序列分析，以及 2)确定从人和伴侣动物分离的ESBL-E的相关性 在相似的时间段内和相同的地理位置按基因组分离的感染 序列分析我们在2018年至2021年期间发现了60种临床ESBL-E， 人类和伴侣动物在弗吉尼亚州西南部，并已部分特征， 通过鉴定ESBL基因分离菌株。我们建议进行短读全基因组测序 (WGS)弗吉尼亚理工大学动物实验室服务中心的这些分离物， 实验室执行和解释WGS的能力。将对测序数据进行评价， 抗性基因和多位点序列（MLST）分析。相同的MSPs类型的分离株将 进行单核苷酸多态性分析，以确定生物体的相关性。 监测耐药病原体的区域特定种群动态， 实施与当地有关的缓解战略，改善动物和人类健康， 从而直接支持Vet-LIRN保护人类和动物健康的使命， 提高我们实验室应对Vet-LIRN调查的能力， 人类和动物的食物。

Project Summary Antimicrobial resistance is a major threat to public health worldwide. The Centers for Disease Control and Prevention has identified extended spectrum beta lactamase-producing Enterobacterales (ESBL-E) as a serious threat to public health, and these organisms cause clinical infections in humans and a variety of veterinary species, including dogs and cats. Therefore, it is essential to adopt a “One Health” approach to understand and combat antimicrobial resistance. In addition, fecal carriage of the same strain of ESBL-E. coli has been demonstrated to be shared between humans and pets in the same household. However, the relationship between clinical isolates of ESBL-E isolated from infections in pets and people on a population level is unclear. The aims of this study are to: 1) expand capacity of Virginia Tech Animal Laboratory Services to perform whole genome sequencing and sequence analysis, and 2) determine the relatedness of ESBL-E isolated from both of human and companion animal infections isolated over a similar time-period and in the same geographic locations by genome sequence analysis. We have identified 60 clinical ESBL-E isolated between 2018 and 2021 from humans and companion animals in southwestern Virginia and have partially characterized those isolates by identifying ESBL genes. We propose to perform short-read whole genome sequencing (WGS) on those isolates at Virginia Tech Animal Laboratory Services in order to improve our laboratory’s capacity to perform and interpret WGS. Sequencing data will be evaluated for resistance gene and multilocus sequence (MLST) analysis. Isolates of the same MSLT type will undergo single-nucleotide polymorphism analysis to determine the relatedness of the organisms. Monitoring of regionally-specific population dynamics of drug-resistant pathogens allows for implementation of locally-relevant mitigation strategies that improve animal and human health, thereby directly supporting the Vet-LIRN mission to safeguard human and animal health and to increase our laboratory’s capacity to respond to Vet-LIRN investigations and enhance the safety of human and animal foods.