Booth M C, Atkuri R V, Nanda S K, Iandolo J J, Gilmore M S
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Invest Ophthalmol Vis Sci. 1995 Aug;36(9):1828-36.
To evaluate the contribution of toxins to the severity of Staphylococcus aureus endophthalmitis.
Experimental endophthalmitis was established by injecting rabbit eyes with wild type S. aureus ISP479 and the isogenic attenuated strain, ISP546, defective in expression of the global regulator locus agr. agr regulates expression of at least 19 exoproteins that are potentially important in the pathogenesis of endophthalmitis. Infections were evaluated using electroretinography, slit lamp biomicroscopy, and histology. Two concentrations (approximately 10 and 1000 organisms) of bacteria were injected.
The agr- strain consistently resulted in slower loss of b-wave response when compared to the wild type strain, irrespective of inoculum size. Clinical signs were less severe among the agr- group at 24 and 48 hours when 10 organisms were injected. However, when the number of bacteria injected was increased to 1000, earlier onset of clinical signs was observed, with both groups showing maximum cell and flare and a white fundal reflex at 48 hours after infection. Histologic examination of eyes enucleated 36 hours after inoculation revealed that the wild type strain induced focal retinal destruction and mild vitritis, whereas eyes infected with the agr- strain remained completely normal. Histologic examination carried out when loss of B-wave response was 100% revealed that retinal changes for both groups could not be distinguished.
These data indicate that toxin production by S. aureus contributes to severity of endophthalmitis by accelerating the rate of onset of retinal damage. Therefore, toxin-targeting therapies instituted early in the course of infection could preserve retinal function.
评估毒素对金黄色葡萄球菌性眼内炎严重程度的影响。
通过向兔眼注射野生型金黄色葡萄球菌ISP479和同源减毒株ISP546建立实验性眼内炎，ISP546在全局调节基因座agr的表达上存在缺陷。agr调节至少19种外毒素的表达，这些外毒素在眼内炎发病机制中可能具有重要作用。使用视网膜电图、裂隙灯生物显微镜检查和组织学评估感染情况。注射两种浓度（约10个和1000个菌体）的细菌。
无论接种量大小，与野生型菌株相比，agr缺陷菌株导致b波反应丧失的速度始终较慢。当注射10个菌体时，agr缺陷组在24小时和48小时时临床症状较轻。然而，当注射的细菌数量增加到1000个时，观察到临床症状出现更早，两组在感染后48小时均出现最大细胞和闪光以及白色眼底反射。对接种后36小时摘除的眼球进行组织学检查发现，野生型菌株引起局灶性视网膜破坏和轻度玻璃体炎，而感染agr缺陷菌株的眼球则完全正常。在b波反应丧失100%时进行的组织学检查显示，两组视网膜变化无法区分。
这些数据表明，金黄色葡萄球菌产生的毒素通过加速视网膜损伤的发生速度，导致眼内炎严重程度增加。因此，在感染过程早期采用靶向毒素的治疗方法可以保护视网膜功能。
