Interaction between s. aureus and bovine mammary epithelial cells

在乳制品行业，乳腺炎是一种代价最高的疾病，它会给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可能会引起食品安全问题。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。金黄色葡萄球菌乳腺炎具有传染性且极难控制，因为它通常发展为慢性感染，因为它们能够粘附、侵入并持续存在于乳腺上皮细胞中。乳内感染的金黄色葡萄球菌菌株产生几种细胞表面相关产物。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。本研究的总体目标是利用金黄色葡萄球菌表面蛋白ClfA作为模型系统，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。具体来说，本研究旨在回答以下问题：来自不同金黄色葡萄球菌菌株的ClfA重复序列长度的变化如何影响其与上皮细胞的结合？不同的培养条件对重复序列的表达有何影响？ClfA是否通过其他蛋白质或作为上皮细胞受体的配体连接细菌和宿主上皮细胞？是否有可能鉴定和分离牛上皮细胞上的受体？金黄色葡萄球菌和牛上皮细胞在相互作用过程中基因表达是如何变化的？本研究结果将揭示金黄色葡萄球菌的致病机制，从而为更好的预防和治疗方案提供新的策略。

In the dairy industry, mastitis is a most costly disease that causes significant losses in economics and milk production. As well, mastitis is an animal welfare issue and use of antibiotics to treat mastitis could be a concern for food safety. While many bacteria can cause bovine mastitis, one of the major causes is Staphylococcus aureus. S. aureus mastitis is contagious and extremely difficult to control because it usually develops into a chronic infection, due to their ability to adhere, invade, and persist in mammary epithelial cells. S. aureus strains from intramammary infection produce several 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 global objective of this proposed research is to use ClfA, a surface protein on S. aureus,  as a model system 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: how does the varying length of the repeats in ClfA from different strains of S. aureus affect the binding to epithelial cells? How do the different culture conditions affect the expression of repeats? Does ClfA link the bacteria and host epithelial cells through other proteins or as a ligand to the epithelial cell receptors? Is it possible to identify and isolate the receptors on bovine epithelial cells? How does gene expression change in both S. aureus and bovine epithelial cells during their interactions? Results from this proposed study will shed light on pathogenic mechanisms of S. aureus and consequently provide new strategies for a better prevention and therapy program.