Dairy niche adaptation by bovine mastitis pathogens: novel targets for control

乳腺炎（乳腺感染）是一个重要的动物福利问题，也是全球乳制品行业的主要经济负担。由于细菌生物膜形成、细胞内存活和抗生素耐药性，抗生素治疗通常无效。迫切需要抗生素的替代品，但合理设计新的治疗方法需要提高对细菌如何引起疾病的机制的理解。一系列细菌病原体可引起牛乳房炎，包括一些适应于在乳制品环境中生存和传播的细菌病原体。例如，我们已经发现几种主要的乳腺炎病原体，包括金黄色葡萄球菌和无乳链球菌，表现出与诱导乳中凝结的能力相关的生长增强，并产生乳依赖性生物膜表型。值得注意的是，这些表型与人类S不相同。aureus或S.无乳分离物与乳制品生态位适应一致。在这里，使用群体水平和分子功能技术相结合，我们将研究支持S。金黄色葡萄球菌在乳制品环境中生存和增殖。特别是，我们将剖析一种新的牛奶依赖性生物膜表型的基础，并研究其相关性的发病机制和抗生素治疗的弹性。该研究将揭示牛沙门氏菌所需的关键生物学途径和/或组分。金黄色葡萄球菌在乳制品环境中存活，这可能代表控制感染的新靶点。将使用特异性抗体方法和由栖息在奶牛微生物群中的其他细菌物种产生的新型抗生物膜剂来研究奶牛适应性性状控制乳腺炎的治疗靶向潜力。

Mastitis (infection of the mammary gland) is an important animal welfare issue and a major economic burden on the global dairy industry. Treatment with antibiotics is often ineffective due to bacterial biofilm formation, intra-cellular survival and antibiotic resistance. Alternatives to antibiotics are urgently needed but rational design of new therapeutic approaches requires improved mechanistic understanding of how bacteria cause disease. An array of bacterial pathogens can cause bovine mastitis including some that are adapted to survive and transmit in the dairy environment. For example, we have discovered that several major mastitis pathogens including Staphylococcus aureus, and Streptococcus agalactiae demonstrate enhanced growth associated with the ability to induce curdling in milk, and produce a milk-dependent biofilm phenotype. Of note, these phenotypes are not shared with human S. aureus or S. agalactiae isolates consistent with dairy niche adaptation. Here, using a combination of population level and molecular functional techniques, we will investigate key mechanisms supporting the ability of S. aureus to survive and proliferate within the dairy environment. In particular, we will dissect the basis for a novel milk-dependent biofilm phenotype, and investigate its relevance to pathogenesis and resilience to antibiotic treatment. The study will reveal key biological pathways and/or components required by bovine S. aureus to survive in the dairy environment which could represent novel targets for control of infection. The potential for therapeutic targeting of dairy adaptive traits for control of mastitis will be investigated using a specific antibody approach and novel anti-biofilm agents produced by other bacterial species that inhabit the dairy bovine microbiota.