Streptococcus pneumoniae ocular pathogenesis and therapy

肺炎链球菌眼部发病机制及治疗

• 批准号: 7494191
• 负责人: MARY E MARQUART
• 金额: $ 5.53万
• 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/7494191
• 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; Purpose; 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; killings; mutant; neutrophil; novel; pathogen; prevent; programs; success; vision science

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.

肺炎链球菌是细菌性角膜炎的主要原因。肺炎球菌角膜炎 造成的损害可能导致不可逆转的角膜疤痕。角膜损伤可见于 肺炎球菌性角膜炎主要是由于细菌毒力因子刺激 强烈的宿主反应。对于肺炎球菌角膜炎来说，重要的是肺炎球菌溶血素的产生，这是一种 能够裂解细胞以及激活补体的毒力因子。在非眼科 感染时，肺炎球菌溶血素的产生不足以达到毒力；有机体必须 还生产多糖胶囊。胶囊在角膜炎或其他眼部疾病中的作用 感染尚未确定，该实验室的初步数据表明 胶囊可能不会导致眼毒力。这一点很重要，因为疫苗接种 已建议将其作为预防肺炎球菌眼部感染的一种方法。 拟议的研究旨在开发限制与相关损害相关的方法 肺炎球菌角膜炎。这项研究包括使用针对 毒力因子负责保护有机体并刺激有害物质 炎症反应。直接目标是：1）确定胶囊是否具有毒力 角膜炎的一个因素，一项研究可能表明，与血管化的身体部位不同，角膜是 易受未包膜菌株感染； 2) 确定是否抑制肺炎球菌溶血素 局部应用抑制其与细胞结合的分子将提供保护 受感染的角膜发炎，初步研究支持这种可能性；和 3) 确定是否可以主动或被动使用肺炎球菌溶血素抗体来限制或预防这种能力 该分子诱导炎症并产生组织损伤作用。 从公共卫生的角度来看，包括肺炎球菌在内的细菌正变得越来越多 对抗生素有耐药性。细菌眼替代疗法和新型疗法的开发 感染将有助于防止留下疤痕和失去眼睛。