Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3187-92. doi: 10.1167/iovs.10-6558.
Wall teichoic acids (WTAs) are major polyanionic polymer components of the cell wall of Staphylococcus aureus. However, little is known about their role at the host-pathogen interface, especially in endophthalmitis. This study was designed to investigate the extent to which WTAs contribute to the pathogenicity of S. aureus in models of endophthalmitis and to determine whether there would be value in targeting their biosynthesis as a new therapeutic approach.
S. aureus RN6390 and its isogenic WTA-null mutant (RN6390ΔtarO) were used to evaluate the role of WTAs in endophthalmitis. RN6390 and RN6390ΔtarO were cultured in bovine vitreous humor (VH) in vitro or inoculated into the vitreous chamber of C57B6 mice. Changes in the number of bacteria, organ function as determined by electroretinography (ERG), and histopathologic changes were assessed throughout the course of infection. In addition, the efficacy of WTA biosynthesis inhibitors in VH in vitro was examined.
It was observed that a component of VH synergized with WTA biosynthesis inhibitors in vitro and killed the S. aureus. This effect was also seen when mutants incapable of expressing WTA were exposed to VH. The killing activity of VH was lost on treatment with a protease inhibitor. RN6390ΔtarO could not survive in mouse eyes and did not affect organ function, nor was it able to establish endophthalmitis.
WTAs are essential cellular constituents for the manifestation of virulence by S. aureus in endophthalmitis, and appears to be a viable target for treating the endophthalmitis caused by S. aureus strains.
壁磷壁酸（WTAs）是金黄色葡萄球菌细胞壁的主要多阴离子聚合物成分。然而，人们对其在宿主-病原体界面的作用知之甚少，特别是在眼内炎中。本研究旨在调查 WTA 在金黄色葡萄球菌眼内炎模型中的致病性中的作用，并确定针对其生物合成作为新的治疗方法是否有价值。
使用金黄色葡萄球菌 RN6390 及其同工型 WTA 缺失突变体（RN6390ΔtarO）来评估 WTA 在眼内炎中的作用。在体外牛玻璃体（VH）中培养 RN6390 和 RN6390ΔtarO 或接种到 C57B6 小鼠的玻璃体腔中。在整个感染过程中，评估细菌数量的变化、电视网膜图（ERG）确定的器官功能以及组织病理学变化。此外，还检查了 VH 中 WTA 生物合成抑制剂的疗效。
观察到 VH 的一个成分与 WTA 生物合成抑制剂在体外协同作用并杀死金黄色葡萄球菌。当无法表达 WTA 的突变体暴露于 VH 时，也观察到这种效应。VH 的杀菌活性在用蛋白酶抑制剂处理后丧失。RN6390ΔtarO 无法在小鼠眼中存活，也不会影响器官功能，也无法引起眼内炎。
WTAs 是金黄色葡萄球菌在眼内炎中表现毒力所必需的细胞成分，似乎是治疗金黄色葡萄球菌引起的眼内炎的可行靶点。
