Adherence and Colonization in Keratitis

描述：据估计，美国每年约有3万例细菌性角膜炎，全球约有10万例。非手术创伤和隐形眼镜佩戴是导致微生物角膜炎的主要危险因素。长时间佩戴隐形眼镜导致患者易患角膜炎的机制仍存在争议。隐形眼镜引起的缺氧被用来解释与佩戴隐形眼镜相关的眼部并发症。然而，高透氧镜片已被引入，但似乎并没有显著减少并发症的发生率。角膜上皮屏障功能的非特异性下降可能是机械性的，源于闭眼佩戴时隐形眼镜下碎片的积累，以及睁眼佩戴时正常眨眼的摩擦和压力。不管触发因素是什么，微生物对受伤角膜的粘附能力都增强了。粘附机制，粘附微生物的命运，上皮细胞的反应，或负责粘附和定植的特定细菌因子的作用，直到现在才出现角膜炎的主要原因，即金黄色葡萄球菌引起的角膜炎。因此，我们建议进行实验来验证以下假设：1)金黄色葡萄球菌使用特定的基质或细胞表面结合蛋白在伤口部位结合暴露的上皮细胞表面或沉积的细胞外基质蛋白；2)表达某些性状（可能包括生物膜形成等定植性状）的致病性谱系在角膜炎分离株中丰富；3)金黄色葡萄球菌毒素的表达扰乱了原本良好平衡的先天宿主反应，使其效率低下，从而使金黄色葡萄球菌得以定植和感染。

DESCRIPTION: It is estimated that approximately 30,000 cases of microbial keratitis occur annually in the U.S. and 100,000 cases globally. Non-surgical trauma and contact lens wear are the leading predisposing risk factors for microbial keratitis. The mechanisms that predispose patients to keratitis as the result of extended contact lens wear remain the subject of controversy. Contact lens induced hypoxia has been used to explain the ocular complications associated with contact lens wear. However, highly oxygen permeable lenses have been introduced, but do not appear to significantly reduce the complication rate. The non-specific decrease in corneal epithelial barrier function may be mechanical in origin, stemming from the accumulation of debris underneath the contact lens during closed-eye wear, and friction and pressure from normal blinking during open eye wear. Irrespective of the trigger, microbes display enhanced adherence to wounded cornea. The mechanisms of adherence, the fate of adherent microbes, the response of epithelial cells, or the role of specific bacterial factors responsible for adherence and colonization are only now emerging for a leading cause of keratitis, namely that caused by S. aureus. We therefore propose to conduct experiments to test the following hypotheses: 1) that S. aureus uses specific matrix- or cell surface- binding proteins to bind exposed epithelial cell surfaces, or deposited extracellular matrix proteins, at the site of a wound; 2) that pathogenic lineages expressing certain constellations of traits, possibly colonization traits including biofilm formation, are enriched among keratitis isolates; and 3) that the expression of toxins by S. aureus deranges an otherwise finely balanced innate host response, rendering it inefficient and thereby allowing S. aureus to colonize and infect.