SIGNIFICANCE OF CORNEAL CELL INVASION BY BACTERIA

描述（改编自申请人摘要）：铜绿假单胞菌可 会导致危及视力的角膜感染多种抗生素的出现 对这种微生物的抗性表明需要新的方法来控制 铜绿假单胞菌感染在以前的研究中，研究者 证明侵袭性铜绿假单胞菌菌株可以侵入角膜， 上皮细胞，突破内吞空泡，在这些细胞内复制， 最终杀死宿主细胞。长期目标是 项目是确定是否阻止角膜细胞的侵袭假单胞菌 铜绿假单胞菌可用于治疗性或预防性干预。到 确定细菌入侵的机制及其在 疾病，将测试以下假设：特定的细菌基因 调节铜绿假单胞菌的侵袭和该病原体的内化 涉及利用宿主细胞粘着斑复合物（FAC）信号传导。 具体目标1是鉴定调节细胞凋亡的特定细菌基因。 铜绿假单胞菌入侵，并测试突变体和/或 在体内侵入能力改变的转移接合物。具体 目的2是确定FAC信号传导在体外侵袭中的作用， vivo.拟议的研究将提供新的洞察机制， 铜绿假单胞菌对角膜细胞的侵袭作用及其在 疾病，这可能导致新的策略，治疗铜绿假单胞菌 眼部和非眼部感染。

DESCRIPTION (Adapted from applicant's abstract): Pseudomonas aeruginosa can cause sight-threatening corneal infection. The emergence of multiple antibiotic resistance to this organism suggests that new approaches are needed for control of Pseudomonas aeruginosa infections. In previous studies, the investigator has demonstrated that invasive Pseudomonas aeruginosa strains can invade corneal epithelial cells, break out of the endocytic vacuole, replicate within these cells, and eventually they kill the host cell. The long-term goal of this project is to determine if blocking corneal cell invasion by Pseudomonas aeruginosa could be used for therapeutic or preventative intervention. To determine the mechanisms involved in bacterial invasion and their role in disease, the following hypothesis will be tested: specific bacterial genes modulate Pseudomonas aeruginosa invasion and internalization of this pathogen involves exploitation of host cell focal adhesion complex (FAC) signaling. Specific aim 1 is to identify specific bacterial genes that modulate Pseudomonas aeruginosa invasion, and to test the virulence of mutants and/or transconjugants that are altered in their ability to invade in vivo. Specific aim 2 is to determine the role of FAC signaling in invasion in vitro and in vivo. The proposed studies will provide new insight into the mechanisms of corneal cell invasion by Pseudomonas aeruginosa and of the role of invasion in disease, which could lead to new strategies for treating Pseudomonas aeruginosa ocular and non-ocular infections.