Adherence and Colonization in Keratitis

描述：据估计，美国每年约有30,000例微生物角膜炎发生，全球每年有100,000例。非手术创伤和配戴隐形眼镜是细菌性角膜炎的主要易感因素。由于长时间配戴隐形眼镜，导致患者患角膜炎的机制仍然存在争议。隐形眼镜引起的低氧已被用来解释与配戴隐形眼镜相关的眼部并发症。然而，已经引入了高透氧性镜片，但似乎并不能显著降低并发症发生率。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面堆积的碎片，以及睁眼佩戴时正常眨眼时的摩擦和压力。无论触发因素如何，微生物对受伤的角膜表现出更强的粘附性。黏附机制、黏附微生物的命运、上皮细胞的反应或负责黏附和定植的特定细菌因素的作用直到现在才出现，导致角膜炎的一个主要原因是金黄色葡萄球菌。因此，我们建议进行实验来检验以下假设：1)金黄色葡萄球菌使用特定的基质或细胞表面结合蛋白来结合暴露的上皮细胞表面，或在伤口部位沉积细胞外基质蛋白；2)表达某些特征的病原体谱系，可能包括生物膜形成的定植特征，在角膜炎分离株中丰富；以及3)金黄色葡萄球菌毒素的表达扰乱了原本平衡的先天宿主反应，使其效率低下，从而允许金黄色葡萄球菌定居和感染。

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.