Interaction between S. aureus and bovine mammary epithelial cells

在乳制品行业，乳腺炎是成本最高的疾病，对经济和牛奶生产造成重大损失。此外，乳腺炎是一个动物福利问题，使用抗生素治疗乳腺炎涉及食品和环境安全。虽然许多细菌可以引起牛乳腺炎，其中一个主要原因是金黄色葡萄球菌（金黄色葡萄球菌）。金黄色葡萄球菌乳腺炎具有传染性且极难控制，因为金黄色葡萄球菌粘附、侵入并持续存在于乳腺上皮细胞中，通常发展为慢性感染。来自乳腺内感染的金黄色葡萄球菌菌株产生许多细胞表面相关产物。大多数产物的确切致病作用及其对粘附和侵袭的影响尚未得到很好的评价。我们也知道乳腺上皮细胞相关分子在乳腺炎发病过程中与金黄色葡萄球菌相互作用，但它们在粘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。本研究的总体目标是利用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侵袭牛乳腺上皮细胞的机制以及上皮细胞对感染的反应。具体而言，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是如何变化的？(2)不同菌株或分离株的金黄色葡萄球菌ClfA重复序列长度的变化如何影响其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受体？本研究结果将进一步揭示金黄色葡萄球菌的致病机制，从而为牛乳腺炎的预防、治疗和管理提供新的策略。预计这项研究不会导致任何疫苗的开发。尽管如此，本研究项目必将有助于我们对金黄色葡萄球菌与牛乳腺相互作用的基本认识。

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.