Novel approaches to prevent bovine mastitis by microbiome manipulation - Nouvelles approches en matière de prévention de la mammite bovine par la manipulation du microbiome

牛乳腺炎是一种复杂的疾病，是乳制品生产中成本最高的问题之一，导致加拿大乳制品行业每年净损失至少6.65亿美元。这在魁北克省和安大略省是一个特别重要的问题，这两个省加起来饲养了加拿大大约70%的奶牛。牛乳腺炎可分为传染性乳腺炎，这是由致病菌在奶牛之间传播引起的；或者是环境性乳腺炎，病原体是从奶牛生活的环境中获得的。传染性乳腺炎仍然是这种疾病中最严重的类型；然而，在过去的几十年里，传染性乳腺炎的发病率有了很大的下降，而环境性乳腺炎的发病率却有了绝对的增加，这使得后者成为乳制品行业需要解决的一个重要问题。大肠杆菌是环境性乳腺炎最常见的病因。我们使用细菌比较基因组学方法鉴定了一组9个基因，这些基因能够区分无害的共生牛大肠杆菌和能够引起乳腺炎的环境菌株。我们选择了这9个基因中的2个来开发CRISPR-Cas9系统，该系统可以从牛胃肠道系统中去除有问题的大肠杆菌菌株。这是一项创新的战略，以减轻加拿大乳制品行业环境乳腺炎的负担。将这种新产品推向市场的下一步是临床前测试，以确定牛的安全性。在这个项目中，麦吉尔大学、舍布鲁克大学和圭尔夫大学将合作对这项技术进行临床测试。圭尔夫大学的乳制品研究机构将是主要的测试地点。该项目将在牛乳腺炎、下一代测序、生物信息学、比较基因组学和奶牛临床试验等领域培养1名博士后。

Bovine mastitis is a complex disease that is one of the costliest issues in dairy production - resulting in a net-loss of at least $665-million annually from the Canadian Dairy Industry. This is a particularly important problem in the provinces of Quebec and Ontario, which combined house about 70% of the dairy cattle in Canada. Bovine mastitis can be classified as either contagious mastitis, which results from the spread of pathogenic bacteria from cow to cow; or environmental mastitis, in which the pathogens were acquired from the environment in which the cow lives. Contagious mastitis is still the most serious type of this disease; however, in the past few decades there has been a major decrease in the prevalence of contagious mastitis and an absolute increase in the incidence of environmental mastitis, making the latter an important problem for the dairy industry to address. Escherichia coli is the most common cause of environmental mastitis. We have used a bacterial comparative genomics approach to identify a set of 9 genes which are able to differentiate harmless commensal bovine E. coli from environmental strains that are capable of causing mastitis. We chose two of these nine genes to develop a CRISPR-Cas9 system that can remove problematic E. coli strains from the bovine gastrointestinal system. This is an innovative strategy to lessen the burden of environmental mastitis in the Canadian dairy industry. The next step in taking this novel product to market is pre-clinical testing to determine safety in cows. In this project McGill, University of Sherbrooke, and the University of Guelph will partner to clinically test this technology. The dairy research facility at the University of Guelph will be the primary site of testing. This project will train one post-doctoral fellow in bovine mastitis, next-generation sequencing, bioinformatics, comparative genomics, and conducting clinical trials in dairy cattle.