Barequet Irina S, Habot-Wilner Zohar, Mann Oran, Safrin Mary, Ohman Dennis E, Kessler Efrat, Rosner Mordechai
Maurice and Gabriela Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, Israel.
Graefes Arch Clin Exp Ophthalmol. 2009 Jul;247(7):913-7. doi: 10.1007/s00417-009-1061-2. Epub 2009 Mar 12.
Therapy of S. aureus ocular infections is increasingly challenging due to emerging resistant strains. Staphylolysin (also called LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of this study was to evaluate the efficacy of staphylolysin as a therapy for experimental methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis, focusing on its bactericidal activity.
Endophthalmitis was induced in the right eyes of 46 rats by an intravitreal injection of 50-160 MRSA cells. Two therapeutic regimens were evaluated: (i) an intravitreal injection of staphylolysin at 6 hours post-infection; (ii) two successive intravitreal injections of staphylolysin given at 6 and 30 hours post-infection. Control eyes were injected with vehicle alone at the same times. The rats were sacrificed 48 hours after infection, and the vitreous was withdrawn for determination of colony forming units (CFU). Potential adverse effects of intravitreal staphylolysin injection were assessed histopathologically in four uninfected eyes, enucleated from rats sacrificed 1 month after intravitreal staphylolysin injection.
In eyes treated by the single-injection regimen, staphylolysin reduced the mean CFU value per vitreous threefold as compared to control (2,055 +/- 3,144 and 6,432 +/- 6,389 CFU/vitreous, respectively; P = 0.02). The repeated injection protocol was more effective, reducing the mean CFU value per vitreous by two orders of magnitude as compared to control (1,148 +/- 3,096 and 143,519 +/- 151,358 CFU/vitreous, respectively; P = 0.0005). Histopathological analysis showed no structural damage in eyes injected intravitreally with staphylolysin.
Staphylolysin is effective in the treatment of experimental MRSA-induced endophthalmitis in rats, and causes no morphological adverse effects to ocular tissues. Staphylolysin may be beneficial in the treatment of S. aureus endophthalmitis in humans.
由于耐药菌株的出现，金黄色葡萄球菌眼部感染的治疗越来越具有挑战性。葡萄球菌溶素（也称为LasA蛋白酶）是铜绿假单胞菌分泌的一种溶葡萄球菌内肽酶。本研究的目的是评估葡萄球菌溶素作为治疗实验性耐甲氧西林金黄色葡萄球菌（MRSA）眼内炎的疗效，重点关注其杀菌活性。
通过向46只大鼠右眼玻璃体内注射50 - 160个MRSA细胞诱导眼内炎。评估了两种治疗方案：（i）感染后6小时玻璃体内注射葡萄球菌溶素；（ii）感染后6小时和30小时连续两次玻璃体内注射葡萄球菌溶素。对照眼在相同时间仅注射赋形剂。感染后48小时处死大鼠，抽取玻璃体以测定菌落形成单位（CFU）。在玻璃体内注射葡萄球菌溶素1个月后处死的大鼠摘除的4只未感染眼中，通过组织病理学评估玻璃体内注射葡萄球菌溶素的潜在不良反应。
在单注射方案治疗的眼中，与对照相比，葡萄球菌溶素使每个玻璃体的平均CFU值降低了三倍（分别为2,055±3,144和6,432±6,389 CFU/玻璃体；P = 0.02）。重复注射方案更有效，与对照相比，每个玻璃体的平均CFU值降低了两个数量级（分别为1,148±3,096和143,519±151,358 CFU/玻璃体；P = 0.0005）。组织病理学分析显示，玻璃体内注射葡萄球菌溶素的眼睛没有结构损伤。
葡萄球菌溶素对大鼠实验性MRSA诱导的眼内炎治疗有效，且对眼组织无形态学不良反应。葡萄球菌溶素可能对治疗人类金黄色葡萄球菌眼内炎有益。
