Streptococcus pneumoniae ocular pathogenesis and therapy

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 会导致不可逆转的角膜瘢痕。角膜的损伤 肺炎球菌性角膜炎主要归因于细菌毒力因子， 强烈的宿主反应肺炎球菌性角膜炎的重要因素是肺炎球菌溶血素的产生， 能够裂解细胞以及激活补体的毒力因子。在非眼部 感染时，肺炎球菌溶血素的产生不足以达到毒力;该生物体必须 还产生多糖胶囊。胶囊在角膜炎或其他眼部疾病中的作用 感染尚未建立，该实验室的初步数据表明， 胶囊可能对眼部毒性没有贡献。这一点很重要，因为接种疫苗 已建议将其作为预防肺炎球菌眼部感染的手段。 拟议的研究旨在开发限制与下列因素相关的损害的方法： 肺炎球菌性角膜炎这项研究包括使用新的治疗方法， 毒力因子负责保护生物体和刺激破坏 炎症反应。目前的目标是：1）确定胶囊是否具有毒性 一项研究表明，角膜与血管化的身体部位不同， 易受未包囊化菌株感染; 2）确定是否通过 局部施用抑制其与细胞结合的分子将提供针对以下疾病的保护： 受感染角膜的炎症，初步研究支持这种可能性;以及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阻止 这种分子的作用是诱导炎症并造成组织损伤。 从公共卫生的角度来看，包括肺炎球菌在内的细菌越来越多， 对抗生素有抵抗力细菌性眼的替代疗法和新疗法的发展 感染将有助于防止疤痕和眼睛的损失。

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.