Streptococcus pneumoniae ocular pathogenesis and therapy

描述：肺炎链球菌是细菌性角膜炎的主要原因。肺炎球菌性角膜炎造成的损害可能导致不可逆转的角膜疤痕。肺炎球菌性角膜炎的角膜损害主要归因于刺激宿主强烈反应的细菌毒力因子。肺炎球菌角膜炎的重要作用是产生肺炎溶血素，这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，肺炎溶血素的产生不足以实现毒力；生物体还必须产生多糖囊。该胶囊在角膜炎或其他眼部感染中的作用尚未确定，来自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，因为给患者接种疫苗已被认为是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。这项研究包括针对负责保护有机体和刺激破坏性炎症反应的毒力因子使用新的治疗方法。近期的目标是：1)确定该胶囊是否是角膜炎的致病因子，这项研究可能表明，与有血管的身体部位不同，角膜容易受到未包裹的细菌的感染；2)通过局部应用抑制其与细胞结合的分子来抑制肺炎毒素，是否将提供保护，使其免受感染的角膜的炎症，这一可能性得到了初步研究的支持；以及3)确定是否可以主动或被动地使用针对肺炎毒素的抗体来限制或防止该分子引发炎症并对组织造成损害的能力。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抗药性越来越强。针对细菌性眼部感染的替代和新疗法的开发将有助于防止眼睛的疤痕和丧失。

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.