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

牛乳房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的损失估计为6.65亿美元。金黄色葡萄球菌是加拿大和世界范围内引起牛乳房炎的主要原因。金黄色葡萄球菌乳房炎感染令人担忧，因为感染是长期的、反复发生的，很难用抗生素有效地治疗。奶农用抗生素治疗和预防奶牛，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。一些经常在乳头管道和原料奶中定居的细菌与奶牛的感染无关，也可以对抗金黄色葡萄球菌的生长。在早期的工作中，我们鉴定了木质葡萄球菌和尿液气球菌就是两个这样的物种。然而，在某些情况下，木质链球菌和尿曲霉菌也都是牛乳房炎的可疑病原体，目前尚不清楚木质链球菌和尿曲霉菌分离物与宿主的关系类型是由于宿主因素(即免疫状态或年龄)还是特定细菌分离物的潜在毒力差异所致。本项目将尝试回答这个问题。我们推测，筛选出的木霉和尿曲霉菌对金黄色葡萄球菌无致病作用，对金黄色葡萄球菌有拮抗作用，适合预防金黄色葡萄球菌乳房炎。我们提出三个相互关联的具体目标，以回答基本的和应用的问题，这些问题需要现有小组成员的补充专门知识。我们将使用1-全基因组测序来确定木质链霉菌和金黄色葡萄球菌分离株之间是否存在明显的基因组差异；2-体外共培养试验来确定哪些分离株可以直接拮抗金黄色葡萄球菌的生长；以及3-使用小鼠模型来确定来自健康奶牛的分离株是否会导致小鼠乳房炎。该项目将汇集顶尖的研究人员，最终阐明木霉和乌尔奎斯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.