Cholesterol as treatment for pneumococcal keratitis: Cholesterol-specific inhibition of pneumolysin in the cornea
Cholesterol as treatment for pneumococcal keratitis: Cholesterol-specific inhibition of pneumolysin in the cornea
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DOI：
10.1167/iovs.07-0017
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发表时间：
2007-06-01
影响因子：
4.4
通讯作者：
O'Callaghan, Richard J.
中科院分区：
文献类型：
--
作者：
Marquart, Mary E.;Monds, Kathryn S.;O'Callaghan, Richard J.
目的.本研究的目的是确定胆固醇，肺炎链球菌肺炎链球菌溶血素的宿主细胞受体，是否可以有效地治疗肺炎球菌性角膜炎。新西兰白色兔用105个集落形成单位（CFU）的S. pneumoniae D39.从感染后25小时开始，每2小时用1%胆固醇局部滴眼液处理角膜，并在感染后24、36和48小时通过裂隙灯显微镜检查。处死家兔，并在最终裂隙灯检查（SLE）后从角膜回收CFU。进行胆固醇对细菌的最小抑菌浓度（MIC）测定。通过基质内注射含或不含胆固醇的肺炎球菌溶血素，检测了胆固醇对兔角膜中肺炎球菌溶血素的特异性抑制作用，并与使用兔红细胞溶血试验的体外肺炎球菌溶血素的胆固醇抑制作用进行了比较。感染后48小时，用胆固醇处理的角膜的SLE评分显著低于用载体处理的角膜（P = 0.0015）。经处理的角膜也具有显著更少的log。CFU高于溶剂处理的角膜（P = 0.0006）。胆固醇在1%的浓度是杀菌的细菌在体外，和较低浓度的胆固醇的浓度依赖性的方式部分抑制。胆固醇也特异性抑制1 μ g肺炎球菌溶血素在体内和高达50 ng肺炎球菌溶血素在体外。局部应用胆固醇是治疗S.肺炎性角膜炎胆固醇不仅抑制肺炎球菌溶血素，它也是杀菌。
PURPOSE. The purpose of this study was to determine whether cholesterol, the host cell receptor for pneumolysin of Streptococcus pneumoniae, could effectively treat pneumococcal keratitis.METHODS. New Zealand White rabbits were intrastromally injected with 105 colony-forming units (CFUs) of S. pneumoniae D39. Corneas were treated with topical drops of 1% cholesterol every 2 hours beginning 25 hours after infection and were examined by slit lamp microscopy 24, 36, and 48 hours after infection. Rabbits were killed, and CFUs were recovered from the corneas after the final slit lamp examination (SLE). Minimal inhibitory concentration (MIC) assays of cholesterol against bacteria were performed. Specific inhibition of pneumolysin by cholesterol in the rabbit cornea was tested by intrastromal injection of pneumolysin with or without cholesterol and was compared with cholesterol inhibition of pneumolysin in vitro using hemolysis assays with rabbit erythrocytes.RESULTS. Corneas treated with cholesterol had significantly lower SLE scores 48 hours after infection than corneas treated with vehicle (P = 0.0015). Treated corneas also had significantly less log,. CFUs than vehicle-treated corneas (P = 0.0006). Cholesterol at a 1% concentration was bactericidal to bacteria in vitro, and lower concentrations of cholesterol were partially inhibitory in a concentration-dependent manner. Cholesterol also specifically inhibited 1 mu g pneumolysin in vivo and up to 50 ng pneumolysin in vitro.CONCLUSIONS. Topical cholesterol is an effective treatment for S. pneumoniae keratitis. Cholesterol not only inhibits pneumolysin, it is also bactericidal.