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

牛乳腺炎病原体对乳制品生态位的适应：新的控制目标

• 批准号: BB/W014920/1
• 负责人: Ross Fitzgerald
• 金额: $ 68.92万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW014920%2F1
• 关键词: Dairy; niche; adaptation; bovine; mastitis

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.

乳房炎(乳腺感染)是一个重要的动物福利问题，也是全球奶业的主要经济负担。由于细菌生物膜的形成、细胞内存活和抗生素耐药性，抗生素治疗往往无效。迫切需要抗生素的替代品，但合理设计新的治疗方法需要改进对细菌如何导致疾病的机械理解。一系列细菌病原体可以引起牛乳房炎，包括一些适应在奶牛环境中生存和传播的细菌。例如，我们发现几种主要的乳房炎病原体，包括金黄色葡萄球菌和无乳链球菌，表现出促进生长的能力，与诱导牛奶凝结的能力有关，并产生依赖牛奶的生物被膜表型。值得注意的是，这些表型与符合乳制品生态位适应的人金黄色葡萄球菌或无乳链球菌分离株不同。在这里，我们将结合种群水平和分子功能技术，研究支持金黄色葡萄球菌在乳品环境中生存和繁殖的关键机制。特别是，我们将剖析一种新的依赖牛奶的生物被膜表型的基础，并调查其与发病机制和对抗生素治疗的抵抗力的相关性。这项研究将揭示牛金黄色葡萄球菌在乳品环境中生存所需的关键生物学途径和/或成分，这可能是控制感染的新靶点。将使用特定的抗体方法和居住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针对奶牛适应特性控制乳房炎的可能性。

项目成果

Time-lapse mesoscopy of Candida albicans and Staphylococcus aureus dual-species biofilms reveals a structural role for the hyphae of C. albicans in biofilm formation

• DOI: 10.1101/2023.08.31.555792
• 发表时间: 2023-09
• 期刊: Microbiology
• 影响因子: 1.5
• 作者: K. Baxter;Fiona A. Sargison;J. R. Fitzgerald;Gail McConnell;P. Hoskisson

Nanoscaled Discovery of a Shunt Rifamycin from Salinispora arenicola Using a Three-Color GFP-Tagged Staphylococcus aureus Macrophage Infection Assay.

• DOI: 10.1021/acsinfecdis.3c00049
• 发表时间: 2023-08-11
• 期刊: ACS INFECTIOUS DISEASES
• 影响因子: 5.3
• 作者: Pham, Nhan T.;Alves, Joana;Sargison, Fiona A.;Cullum, Reiko;Wildenhain, Jan;Fenical, William;Butler, Mark S.;Mead, David A.;Duggan, Brendan M.;Fitzgerald, J. Ross;La Clair, James J.;Auer, Manfred
• 通讯作者: Auer, Manfred