Wiskur Brandt J, Hunt Jonathan J, Callegan Michelle C
Oklahoma Center for Neuroscience, University of Oklahoma HealthSciences Center, Oklahoma City, Oklahoma, USA.
Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4931-8. doi: 10.1167/iovs.08-2276. Epub 2008 Jun 27.
Klebsiella pneumoniae is a common cause of endogenous bacterial endophthalmitis, a disease that frequently results in a poor visual outcome. Hypermucoviscosity has been identified as a virulence factor among clinical bacteremia isolates of K. pneumoniae. In this study, an experimental murine model of K. pneumoniae endophthalmitis was established, and the role of hypermucoviscosity in its pathogenesis was analyzed.
C57BL/6J mice were intravitreously injected with 100 CFU of hypermucoviscous (HMV+) or nonhypermucoviscous (HMV-) K. pneumoniae. Intraocular bacterial growth, retinal function, gross pathology, and inflammatory responses were monitored every 3 hours until the eyes lost significant (>90%) retinal function, or the infection appeared to clear.
The HMV+ strain grew logarithmically in eyes until approximately 15 hours postinfection (PI), reaching a stationary phase of growth at approximately 8.0 log(10) CFU/eye. The HMV- strain grew logarithmically to approximately 7.6 log(10) by 18 hours, but bacterial count declined to approximately 6.4 log(10) CFU/eye by 21 hours PI. Eyes infected with the HMV+ strain retained approximately 35% a-wave and <10% b-wave function by 18 hours PI. These eyes also had a cumulative clinical score of 14+ by 18 hours and underwent phthisis between 21 and 24 hours. Eyes infected with the HMV- strain had a cumulative clinical score of <6 and retained >60% a-wave and >50% b-wave function throughout 21 hours. Five of 7 eyes had <100 CFU HMV- K. pneumoniae at 27 hours PI.
The findings demonstrate the site-threatening consequences of K. pneumoniae endophthalmitis and the importance of the hypermucoviscosity phenotype in the pathogenesis of experimental K. pneumoniae endophthalmitis.
肺炎克雷伯菌是内源性细菌性眼内炎的常见病因,这种疾病常常导致不良的视力预后。高黏液性已被确定为肺炎克雷伯菌临床菌血症分离株中的一种毒力因子。在本研究中,建立了肺炎克雷伯菌眼内炎的实验性小鼠模型,并分析了高黏液性在其发病机制中的作用。
向C57BL/6J小鼠玻璃体内注射100 CFU高黏液性(HMV+)或非高黏液性(HMV-)肺炎克雷伯菌。每3小时监测眼内细菌生长、视网膜功能、大体病理学和炎症反应,直至眼睛失去显著(>90%)的视网膜功能,或感染似乎清除。
HMV+菌株在眼内呈对数生长,直至感染后(PI)约15小时,在约8.0 log(10) CFU/眼时达到生长稳定期。HMV-菌株在18小时时呈对数生长至约7.6 log(10),但在感染后21小时细菌计数降至约6.4 log(10) CFU/眼。感染HMV+菌株的眼睛在感染后18小时保留了约35%的a波和<10%的b波功能。这些眼睛在18小时时的累积临床评分为14+,并在21至24小时之间发生眼球痨。感染HMV-菌株的眼睛累积临床评分为<6,在21小时内保留了>60%的a波和>50%的b波功能。7只眼中有5只在感染后27小时时HMV-肺炎克雷伯菌<100 CFU。
研究结果证明了肺炎克雷伯菌眼内炎对眼部构成威胁的后果,以及高黏液性表型在实验性肺炎克雷伯菌眼内炎发病机制中的重要性。