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P. aeruginosa type III secreted effectors in corneal disease

角膜疾病中铜绿假单胞菌 III 型分泌效应子

基本信息

批准号：
8404007
负责人：
Arne Rietsch
金额：
$ 37.29万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8404007
关键词：
ADP Ribose Transferases Acute Address Animal Model Bacteria Blindness Cells Complement Contact Lenses Cornea Corneal Diseases Corneal Stroma Data Development Disease Disease Progression Dose Enzymes Epithelial Cells Extended-Wear Contact Lenses Eye Infections Eye Injuries Genome Grant Immune Immune response Immune system Individual Infection Infection prevention Invaded Keratitis Lead Left Link Lung Mediating Modeling Molecular Mus Neutrophil Infiltration Organism Pathogenesis Patients Peptide Hydrolases Phenotype Phospholipase Pilum Positioning Attribute Production Properdin Proteins Pseudomonas aeruginosa Reporting Research Role Severity of illness Shapes Signal Transduction Site Staging Syringes TLR4 gene TLR5 gene Toll-like receptors Type III Secretion System Pathway Virulence Virulence Factors Visual impairment bacterial genetics chemokine combat corneal epithelium cytotoxic design extracellular in vivo killings macrophage microbial neutrophil prevent research study rho uptake

项目摘要

P. aeruginosa infections are a common cause of corneal disease associated with extended-wear contact lens use here in the US. One of the primary virulence factors P. aeruginosa uses to promote disease is its type III secretion system, a molecular syringe that allows the bacterium to directly inject effector proteins into targeted host cells. The role of type III secretion in corneal disease has not been studied extensively, but initial reports suggest that corneal disease depends on the complement of effectors being expressed by the infecting bacteria. "Cytotoxic" strains expressing the potent phospholipase ExoU rely extensively on type III secretion to promote disease, whereas ExoS-producing "invasive" strains, appear to not rely on type III secretion in order to elicit corneal disease. We have revisited the role of type III secretion in the pathogenesis of corneal disease elicited by ExoS+ "invasive" isolates of P. aeruginosa. Our preliminary data demonstrates that corneal disease relies critically on type III secretion and on the two effectors ExoS and ExoT, in particular. In addition, we provide evidence that the primary role of type III secretion in corneal disease is to stave off killing by infiltrating neutrophils. Accordingly, the focus of this proposal is to determine the role of the individual enzymatic activities of ExoS and ExoT in preventing clearance by neutrophils in vivo. We will correlate these findings with experiments aimed at examining the role of ExoS and ExoT in preventing phagocytic killing by isolated primary neutrophils. We will also examine the difference in pathogenesis between ExoU-expressing "cytotoxic" and ExoS- expressing "invasive" strains of P. aeruginosa in order to determine if any differences can be directly linked to the activities of these two effectors. Understanding the role of effector proteins in corneal disease is an important step towards formulating new strategies for preventing and treating P. aeruginosa infections of the eye.

铜绿假单胞菌感染是与长时间佩戴相关的角膜疾病的常见原因