Optimizing the microbiome of dairy cattle for increased resistance to Staphylococcus aureus colonization

牛乳腺炎是奶牛乳房的细菌感染，导致疼痛的炎症，牛奶产量减少，每年给加拿大奶农造成约6.65亿美元的损失。在加拿大和世界范围内，金黄色葡萄球菌是牛乳腺炎的主要原因。金黄色葡萄球菌乳腺炎感染是令人担忧的，因为感染是持久的，反复发作的，很难有效地用抗生素治疗。奶农对奶牛进行治疗性和预防性的抗生素治疗，试图治疗或预防感染；然而，抗生素耐药性对人类健康的影响是一场日益严重的国际危机，这种做法不太可能无限期地持续下去。一些常见于乳管和生乳的细菌种类与奶牛感染无关，也可以拮抗金黄色葡萄球菌的生长。在早期的工作中，我们确定了木葡萄球菌和尿equi气球菌是两个这样的物种。然而，在某些情况下，木木假单胞菌和尿马假单胞菌也被怀疑是牛乳腺炎的病原，目前尚不清楚木木假单胞菌和尿马假单胞菌与宿主的关系类型是由于宿主因素（即免疫状态或年龄）还是由于特定细菌分离物的潜在毒力差异。本项目将尝试回答这个问题。我们假设木葡萄球菌和尿马葡萄球菌的分离株不具有乳腺致病性，对金黄色葡萄球菌具有拮抗作用，并且是预防金黄色葡萄球菌乳腺炎的合适益生菌。我们提出了三个相互关联的具体目标，为需要现有团队成员的互补专业知识的基本和应用问题提供答案。我们将使用1-全基因组测序来确定木葡萄球菌和尿棘球菌分离株之间是否存在明显的基因组差异；2-体外共培养试验，确定哪些分离株能直接拮抗金黄色葡萄球菌的生长；第三，使用小鼠模型来确定从健康奶牛中分离的乳腺炎是否会引起小鼠的乳腺炎。该项目将汇集顶尖的研究人员，最终阐明木霉和尿霉在乳房健康和疾病中的作用。

Bovine mastitis is bacterial infection in udders of dairy cattle that results in painful inflammation, a reduction in milk production, and costs the dairy farmers of Canada an estimated $665 million annually. Staphylococcus aureus is a leading cause of bovine mastitis both in Canada and world-wide. S. aureus mastitis infections are concerning because infections are long-lasting, recurrent, and difficult to effectively treat with antibiotics. Dairy farmers treat cows therapeutically and prophylactically with antibiotics to attempt to treat or prevent infections; however, the human health effects of antibiotic resistance are a growing international crisis, and it is unlikely that this practice will continue indefinitely. Some bacterial species that routinely colonize the teat canal and raw milk are not associated with infection in the cow and can also antagonize S. aureus growth. In earlier work, we identified Staphylocuccus xylosus and Aerococcus urinaeequi as being two such species. However, in some instances both S. xylosus and A. urinaeequi are also suspected etiological agents of bovine mastitis, and it is unclear if the type of relationship that S. xylosus and A. urinqeequi isolates have with their host is due to host factors (i.e. immune status or age) or underlying differences in virulence potential of the specific bacterial isolate. This project will attempt to answer this question. We hypothesize that select isolates of S. xylosus and A. urinaeequi are not mammary pathogenic, antagonistic towards S. aureus, and suitable probiotics for the prevention of S. aureus mastitis. We propose three interconnected specific objectives to provide answers to fundamental and applied questions necessitating the complementary expertise of the present team members. We will use 1- whole genome sequencing to determine if there are obvious genomic differences between S. xylosus and A. urinqeequi isolates; 2- in vitro co-culture assays to determine which isolates can directly antagonize the growth of S. aureus; and 3- use a mouse model to determine if isolates from healthy cows cause mastitis in mice. This project will bring together top researchers to conclusively elucidate the roles of S. xylosus and A. urinqeequi in udder health and disease.