Staphylococcus aureus is a common bacterial isolate from cases of microbial keratitis. The virulence factors that contribute to its pathogenicity during this disease have not been fully resolved. The aim of the current study was to examine the effects of the extracellular protease Staphopain A on corneal virulence. Two strains were used, one Staph 38 that gives a high pathology score during keratitis and a less virulent strain ATCC 8325-4. The effect of inhibition of Staphopain by general or specific protease inhibitors on adhesion of strains to fibronectin-coated glass or PMMA was determined. This was followed by an analysis of the effect of Staphopain A on the ability of the bacteria to adhere to and invade corneal epithelial cells. Finally, the effect of inhibiting Staphopain A on pathogenesis in a mouse model of keratitis was studied. Staphopain A increased the adhesion of strains to fibronectin–coated substrata and inhibition of Staphopain A reduced adhesion. The inhibition of Staphopain A by staphostatin A significantly decreased both association with and invasion into human corneal epithelial cells by 15-fold for strain Saur38. Inhibition of Staphopain A significantly reduced the pathology associated with S. aureus keratitis, reducing the infecting numbers of bacteria from 1.8x10⁵ to <1x10⁴ cells/cornea (p ≤ 0.001), significantly reducing the corneal pathology score (p ≤ 0.038) and reducing the numbers of infiltrating PMNs. This study shows that Staphopain increases adhesion and invasion of corneal cells due to increasing fibronectin binding and its inhibition has a significant impact on pathogenicity of S. aureus during keratitis.

金黄色葡萄球菌是微生物角膜炎的常见细菌分离株。在这种疾病中导致其致病性的毒力因子尚未完全解决。本研究的目的是检查细胞外蛋白酶Staphopain A对角膜毒性的影响。使用了两种菌株，一种在葡萄膜炎期间病理评分较高的葡萄球菌38和毒性较低的ATCC 8325-4菌株。确定了一般或特定蛋白酶抑制剂对葡萄球菌蛋白酶的抑制作用对菌株粘附于纤连蛋白包被的玻璃或PMMA的影响。随后分析葡萄球菌素A对细菌粘附和侵袭角膜上皮细胞的能力的影响。最后，研究了抑制葡萄球蛋白A对角膜炎小鼠模型发病机理的影响。Staphopain A增加了菌株对纤连蛋白包被的基质的粘附力，抑制Staphopain A降低了粘附力。Staphostatin A对Staphopain A的抑制作用使Saur38菌株与人角膜上皮细胞的缔合和侵袭均显着降低了15倍。抑制Staphopain A可显着降低与之相关的病理金黄色葡萄球菌性角膜炎将细菌的感染数量从1.8x10 ^5个 细胞/角膜减少到<1x10 ^4个细胞（p≤0.001），显着降低了角膜病理评分（p≤0.038）并减少了浸润性PMN的数量。这项研究表明，葡萄红素由于增加了纤连蛋白的结合而增加了角膜细胞的粘附和侵袭，并且其抑制作用对角膜炎期间金黄色葡萄球菌的致病性具有重大影响。