Streptococcus pneumoniae ocular pathogenesis and therapy

肺炎链球菌眼部发病机制及治疗

• 批准号: 7777295
• 负责人: MARY E MARQUART
• 金额: $ 25.05万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7777295
• 关键词: Alternative Therapies; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antibodies; Award; Bacteria; Bacterial Eye Infections; Binding; Cells; Cholesterol; Cicatrix; Clinical; Complement Activation; Conjunctivitis; Cornea; Cytolysis; Data; Development; Disease; Endophthalmitis; Epithelial Cells; Eye; Eye Infections; Goals; Group Meetings; Human; Immune; Immune Sera; Immune response; Immunoglobulin Isotypes; Immunology; In Vitro; Infection; Inflammation; Inflammatory Response; Keratitis; Knowledge; Laboratories; Lead; Mediating; Meningitis; Microbiology; Modeling; Morbidity - disease rate; Ophthalmology; Organism; Oryctolagus cuniculus; Otitis Media; Parents; Pathogenesis; Patients; Phenotype; Pneumococcal Infections; Pneumonia; Polysaccharides; Prevention; Production; Public Health; Publishing; Reagent; Research; Research Personnel; Resistance; Role; Site; Streptococcus pneumoniae; Streptococcus pneumoniae plY protein; Symptoms; Testing; Tissues; Topical application; Vaccination; Vaccines; Virulence; Virulence Factors; Vision; Work; base; capsule; corneal epithelium; corneal scar; design; direct application; effective therapy; killings; meetings; mutant; neutrophil; novel; pathogen; prevent; programs; success; therapy development; vision science

DESCRIPTION: Streptococcus pneumoniae is a major cause of bacterial keratitis. Pneumococcal keratitis causes damage that can result in irreversible corneal scarring. The corneal damage seen in pneumococcal keratitis has been attributed mainly to bacterial virulence factors that stimulate an intense host response. Important to pneumococcal keratitis is the production of pneumolysin, a virulence factor capable of cell lysis as well as the activation of complement. In non-ocular infections, the production of pneumolysin is not sufficient to achieve virulence; the organism must also produce a polysaccharide capsule. The role of the capsule in keratitis or other ocular infections has not been established and preliminary data from this laboratory suggests that the capsule may not contribute to ocular virulence. This point is significant because vaccination of patients has been suggested as a means to prevent pneumococcal ocular infections. The research proposed is designed to develop means to limit the damage associated with pneumococcal keratitis. This research consists of using new therapies directed toward the virulence factors responsible for protecting the organism and stimulating the damaging inflammatory response. The immediate aims are to: 1) determine if the capsule is a virulence factor in keratitis, a study that could show that the cornea, unlike vascularized body sites, is susceptible to infection by unencapsulated strains; 2) determine if the inhibition of pneumolysin by topical application of a molecule that inhibits its binding to cells will provide protection against inflammation to the infected cornea, a possibility that is supported by preliminary studies; and 3) determine if antibody to pneumolysin can be used actively or passively to limit or prevent the ability of this molecule to induce inflammation with tissue damaging effects. From a public health perspective, bacteria including pneumococcus are becoming increasingly resistant to antibiotics. The development of alternative and novel therapies for bacterial eye infections will help to prevent scarring and loss of the eye.

描述：肺炎链球菌是细菌性角膜炎的主要原因。肺炎球菌性角膜炎可导致不可逆的角膜瘢痕形成。在肺炎球菌性角膜炎中观察到的角膜损伤主要归因于刺激强烈宿主反应的细菌毒力因子。肺炎球菌性角膜炎的重要因素是肺炎球菌溶血素的产生，这是一种能够溶解细胞和激活补体的毒力因子。在非眼部感染中，肺炎球菌溶血素的产生不足以实现毒力;该生物体还必须产生多糖荚膜。尚未确定胶囊在角膜炎或其他眼部感染中的作用，该实验室的初步数据表明胶囊可能不会导致眼部毒力。这一点很重要，因为已经建议将患者接种疫苗作为预防肺炎球菌眼部感染的一种手段。这项研究旨在开发限制肺炎球菌性角膜炎相关损害的方法。这项研究包括使用针对负责保护生物体和刺激破坏性炎症反应的毒力因子的新疗法。近期目标是：1）确定囊是否是角膜炎中的毒力因子，该研究可以表明角膜与血管化身体部位不同，对未包封的菌株的感染敏感; 2）确定通过局部应用抑制肺炎球菌溶血素与细胞结合的分子来抑制肺炎球菌溶血素是否会为感染的角膜提供针对炎症的保护，初步研究支持了这种可能性;和3）确定肺炎球菌溶血素的抗体是否可以主动或被动地用于限制或防止该分子诱导具有组织损伤作用的炎症的能力。从公共卫生的角度来看，包括肺炎球菌在内的细菌对抗生素的耐药性越来越强。细菌性眼部感染的替代疗法和新疗法的开发将有助于防止眼部瘢痕形成和丧失。