Streptococcus pneumoniae ocular pathogenesis and therapy

描述：肺炎链球菌是细菌性角膜炎的主要病因。肺炎球菌性角膜炎造成的损害可导致不可逆的角膜瘢痕。肺炎球菌性角膜炎所见的角膜损伤主要归因于刺激宿主强烈反应的细菌毒力因子。肺炎球菌性角膜炎的重要因素是溶肺素的产生，溶肺素是一种能够分解细胞和激活补体的毒力因子。在非眼部感染中，溶血素的产生不足以达到毒力；生物体还必须产生多糖胶囊。该胶囊在角膜炎或其他眼部感染中的作用尚未确定，该实验室的初步数据表明，该胶囊可能不会导致眼部毒力。这一点很重要，因为已建议患者接种疫苗作为预防肺炎球菌眼部感染的一种手段。提出的研究旨在开发限制与肺炎球菌性角膜炎相关的损害的方法。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。目前的目标是：1)确定胶囊是否是角膜炎的毒力因子，这项研究可能表明，与血管化的身体部位不同，角膜容易被未包被的菌株感染；2)确定局部应用一种抑制溶血素与细胞结合的分子来抑制溶血素是否会对受感染的角膜提供抗炎症保护，初步研究支持了这种可能性；3)确定溶血素抗体是否可以主动或被动地限制或阻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。细菌性眼睛感染的替代疗法和新疗法的发展将有助于防止疤痕和眼睛的丧失。

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.