Interaction between S. aureus and bovine mammary epithelial cells

在乳品行业，乳房炎是最昂贵的疾病，在经济和牛奶生产方面造成重大损失。此外，乳房炎是一个动物福利问题，使用抗生素治疗乳房炎关系到食品和环境安全。虽然许多细菌都能引起牛乳房炎，但主要原因之一是金黄色葡萄球菌(S.aureus)。金黄色葡萄球菌乳房炎具有传染性，极难控制，因为金黄色葡萄球菌能够在乳腺上皮细胞中黏附、入侵和持续存在，通常会发展成一种慢性感染。来自乳腺内感染的金黄色葡萄球菌菌株能产生许多与细胞表面相关的产物。大多数产品的确切致病作用及其对黏附和侵袭的影响尚未得到很好的评估。乳腺上皮细胞相关分子在乳房炎发病机制中与金黄色葡萄球菌相互作用也已为人所知，但其在黏附和侵袭中的作用尚未明确。金黄色葡萄球菌与牛乳腺的相互作用非常复杂。这项研究的总体目标是以金黄色葡萄球菌表面蛋白ClfA作为模型分子，研究金黄色葡萄球菌表面粘附素附着和入侵牛乳腺上皮细胞的机制以及上皮细胞对感染的反应。具体地说，本研究旨在回答以下问题：(1)金黄色葡萄球菌和牛乳腺上皮细胞在相互作用过程中基因表达如何变化？(2)不同菌株或分离株的ClfA重复序列的不同长度如何影响与乳腺上皮细胞的结合和侵袭？(3)是否有可能鉴定和分离牛乳腺上皮细胞上的受体？这项拟议的研究结果将进一步阐明金黄色葡萄球菌的致病机制，从而为更好地预防、治疗和管理牛乳房炎提供新的策略。预计这项研究不会导致任何疫苗的开发。然而，这项研究计划肯定会有助于我们对金黄色葡萄球菌与牛乳腺之间相互作用的基本了解。

In the dairy industry, mastitis is the most costly disease that causes significant losses in economic and milk production terms. As well, mastitis is an animal welfare issue and use of antibiotics to treat mastitis is of concern for food and environmental safety. While many bacteria can cause bovine mastitis, one of the major causes is Staphylococcus aureus (S. aureus). S. aureus mastitis is contagious and extremely difficult to control because it usually develops into a chronic infection due to the ability of S. aureus to adhere, invade, and persist in mammary epithelial cells. S. aureus strains from intramammary infection produce many cell surface-associated products. The exact pathogenic roles of most of the products and their effects on adhesion and invasion are not well evaluated. It is also known that mammary epithelial cell-associated molecules interact with S. aureus during the pathogenesis of mastitis, but their roles on adhesion and invasion have not been characterized. The interaction between S. aureus and bovine mammary glands is very complex. The global objective of this proposed research is to use ClfA, a surface protein on S. aureus, as a model molecule to study the mechanisms by which surface adhesins of S. aureus attach to and invade bovine mammary epithelial cells and how epithelial cells respond to the infection. Specifically, this proposed study aims to answer the following questions: (1) How does gene expression change in both S. aureus and bovine mammary epithelial cells during their interactions? (2) How does the varying length of the repeats in ClfA from different strains or isolates of S. aureus affect the binding and invasion to mammary epithelial cells? (3) Is it possible to identify and isolate the receptors on bovine mammary epithelial cells? Results from this proposed study will shed more light on the pathogenic mechanisms of S. aureus and consequently provide new strategies for a better prevention, therapy program and management of bovine mastitis. It is not envisaged that this research will lead to any vaccine development. Nevertheless, this research program will certainly contribute to our basic understanding of the interaction between S. aureus and the bovine mammary gland.