Traversal mechanism of epithelial cells by P. aeruginosa

铜绿假单胞菌穿越上皮细胞的机制

• 批准号: 7007256
• 负责人: IRANIA ALARCON
• 金额: $ 2.84万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7007256
• 关键词: Pseudomonas aeruginosa; bacteria infection mechanism; cell cell interaction; cornea disorder; corneal epithelium; eye infections; eye movements; fluorescence microscopy; host organism interaction; laboratory mouse; pathologic process; predoctoral investigator; video microscopy

DESCRIPTION (PROVIDED BY APPLICANT): Corneal infection caused by P. aeruginosa (PA) is a sight threatening disease that is difficult to treat. Contact lens wear, the most common predisposing factor for this infection, does not normally cause full thickness epithelial injury to the cornea. Yet little is known about mechanisms that PA use to traverse corneal epithelial cells and reach the underlying stroma. Since traversal represents an early step in pathogenesis, insight into the mechanisms involved could lead to development of preventative measures that completely avoid the devastating effects of PA infection. Twitching motility (tm), a property of bacterial pili, has been found to play a role in corneal infection caused by PA; preliminary data show it is required for traversal across corneal epithelial cells in culture. This project will be focused on the mechanisms by which tm contributes to traversal. The hypothesis to be tested is that tm plays a role in the exit of PA from cells it has invaded and that it is also involved in travel between cells. Exit from corneal epithelial cells will be studied using standard plaque assays, modified gentamicin survival assay and quantitative deconvolution fluorescence microscopy (dm). Extracellular travel will be studied using time-lapse video microscopy and dm.

描述（由申请人提供）：由铜绿假单胞菌 (PA) 引起的角膜感染是一种难以治疗的威胁视力的疾病。佩戴隐形眼镜是这种感染最常见的诱发因素，通常不会导致角膜全层上皮损伤。然而，人们对 PA 穿过角膜上皮细胞并到达底层基质的机制知之甚少。由于遍历代表发病机制的早期步骤，因此深入了解所涉及的机制可能会导致开发预防措施，从而完全避免 PA 感染的破坏性影响。抽搐运动 (tm) 是细菌菌毛的一种特性，已被发现在 PA 引起的角膜感染中发挥作用；初步数据显示，它是穿越培养物中的角膜上皮细胞所必需的。该项目将重点关注 tm 促进遍历的机制。待检验的假设是，tm 在 PA 从其侵入的细胞中排出的过程中发挥作用，并且还参与细胞之间的移动。将使用标准斑块测定、改进的庆大霉素存活测定和定量解卷积荧光显微镜(dm)来研究角膜上皮细胞的退出。将使用延时视频显微镜和 dm 研究细胞外旅行。