Bacteriophages and plasmids in Streptococcus thermophilus

乳制品行业是我们遗产和经济的重要组成部分。它是加拿大农业食品经济的第三大部门，仅次于谷物和红肉。2016年（可获得数据的去年），奶牛养殖业创造了62亿美元的收入，牛奶和乳制品的制成品出货量达到177亿美元。总的来说，乳制品行业占我国食品和饮料行业所有加工销售的15.8%。乳业劳动力包括18,805名奶牛场经营者，而制造业包括22,904个工作岗位，分布在471家加拿大乳品厂。加拿大生产的1050多种奶酪被列入加拿大奶酪目录。去年，加拿大马苏里拉奶酪和披萨奶酪的产量达到了创纪录的水平（148,000公斤，比前一年增长2.0%）。特色奶酪的产量也创历史新高（163,000公斤，比前一年增长5.5%）。没有迹象表明这种生产趋势会改变。然而，我们的乳制品行业面临着国内和国际市场的激烈竞争，必须提供高质量的产品。奶酪制造需要用精心挑选的细菌细胞（发酵剂）接种牛奶，以适当控制发酵并获得高质量的产品。发酵剂是产乳酸菌的组合，其中嗜热链球菌是最重要的一种。有充分的证据表明，在现有的生产设施中，生产力的提高将导致由于细菌病毒（噬菌体）破坏发酵剂而导致牛奶发酵失败。甚至可能需要停产，彻底清理设施。这种自然现象导致产品质量低下和经济损失。因此，持续的噬菌体监测和严格的噬菌体控制措施是必不可少的。关键措施之一是使用抗噬菌体细菌培养物。到目前为止，CRISPR-Cas系统是嗜热葡萄球菌中最重要的噬菌体防御机制，耐crispr噬菌体的嗜热葡萄球菌菌株目前在世界范围内使用。然而，噬菌体正在进化，它们已经找到了绕过CRISPR-Cas防御系统的方法。这个嗜热链球菌的基础研究项目将集中在三个方面：1)噬菌体生物学，2)噬菌体抗性，3)质粒生物学。该基金还将在微生物学、病毒学、生物化学、分子生物学、生物信息学和食品科学等生物科学的各个领域培养几名学生。这一雄心勃勃且最先进的项目将导致对革兰氏阳性细菌中噬菌体-宿主相互作用的最全面分析。这项研究将为我们的加拿大乳制品行业提供基础知识，使他们具有竞争优势。这一知识也将适用于在工业发酵中易受噬菌体攻击的其他细菌菌株。

The dairy industry is a significant part of our heritage and our economy. It is the third largest sector of the Canadian agri-food economy behind grains and red meats. In 2016 (last year for which data are available), dairy farming generated $6.2 billion and manufactured shipments of milk and dairy products equaled $17.7 billion. Overall, the dairy industry accounted for 15.8% of all processing sales in our nation's food and beverage sector. The dairy workforce includes 18,805 dairy farm operators while the manufacturing sector includes 22,904 jobs which are spread into the 471 Canadian dairy factories. Canada produces more than 1,050 cheeses that are listed in the Canadian Cheese Directory. Last year, Mozzarella and pizza cheeses were produced at a record level in Canada (> 148,000 kg, +2.0% from the previous year). A record level was also observed with the production of speciality cheeses (> 163,000 kg, +5.5% from the previous year). There is no indication that this production trend will change. However, our dairy industry faces intense competition in national and international markets and must deliver high-quality products. Cheese manufacture requires the inoculation of milk with carefully selected bacterial cells (starter culture) to properly control the fermentation and to obtain high-quality products. The starter culture is a combination of lactic acid-producing bacteria, from which Streptococcus thermophilus is one of the most important species. It is well documented that increased productivity within existing manufacturing facilities will lead to milk fermentation failures due to bacterial viruses (phages) that destroy the starter cultures. A shut down of production may even be required to thoroughly clean up the facilities. This natural phenomenon leads to low quality products and economic losses. Thus, constant phage monitoring and stringent application of phage control measures are indispensable. One of the key measures is to use phage-resistant bacterial cultures. CRISPR-Cas systems are by far the most important phage defense mechanisms in S. thermophilus and CRISPR-phage-resistant S. thermophilus strains are now used worldwide. However, phages are evolving and they have found ways to bypass the CRISPR-Cas defense systems. This fundamental research program on S. thermophilus will focus on three areas: 1) Phage biology, 2) Phage resistance, and 3) Plasmid biology. This grant will also train several students in various areas of biological sciences such as microbiology, virology, biochemistry, molecular biology, bioinformatics, and food sciences. This ambitious and state-of-the-art program will lead to the most comprehensive analysis of phage-host interactions in a Gram-positive bacterium. This research will provide fundamental knowledge to our Canadian dairy industry to give them a competitive edge. This knowledge will also be applicable to other bacterial strains susceptible to phage attack in industrial fermentations.