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 造成损害，可能导致不可逆转的角膜疤痕。眼角膜的损伤 肺炎球菌性角膜炎主要归因于细菌毒力因子刺激 强烈的宿主反应。肺炎球菌角膜炎的重要作用是产生肺炎溶血素，一种 能够裂解细胞和激活补体的毒力因子。在非眼科 在感染过程中，产生的溶气素不足以产生毒力；生物体必须 还生产了一种多糖胶囊。囊膜在角膜炎或其他眼部疾病中的作用 感染尚未确定，来自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，因为接种疫苗 患者已被建议作为预防肺炎球菌眼部感染的一种手段。 提出的这项研究旨在开发方法，以限制与 肺炎链球菌性角膜炎。这项研究包括使用新的治疗方法来治疗 负责保护有机体和刺激破坏的毒力因子 炎症反应。直接的目的是：1)确定胶囊是否是毒力 角膜炎的因素，一项研究可能表明，角膜，不同于血管化的身体部位，是 容易被无包膜的菌株感染；2)确定是否通过 局部应用抑制其与细胞结合的分子将提供保护 感染的角膜发炎，初步研究支持这种可能性；以及3) 确定是否可以主动或被动地使用肺炎溶血素抗体来限制或防止这种能力 这种分子可以引发炎症，对组织产生破坏作用。 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 对抗生素有抗药性。细菌性眼病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丧失。

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.