Accessory gene regulator controls Staphylococcus aureus virulence in endophthalmitis.

Accessory gene regulator controls Staphylococcus aureus virulence in endophthalmitis.
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发表时间:
1995-08
影响因子:
4.4
通讯作者:
M. C. Booth;R. V. Atkuri;S. Nanda;J. Iandolo;Michael S. Gilmore
M. C. Booth;R. V. Atkuri;S. Nanda;J. Iandolo;Michael S. Gilmore
中科院分区:
医学2区
文献类型:
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作者:
M. C. Booth;R. V. Atkuri;S. Nanda;J. Iandolo;Michael S. Gilmore

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目的探讨毒素对金黄色葡萄球菌眼内炎严重程度的影响。方法用野生型金黄色葡萄球菌ISP479和表达全局调节基因agr缺陷的等基因减毒株ISP546感染兔眼建立实验性眼内炎模型。AGR调节至少19种外源蛋白的表达,这些外源蛋白在眼内炎的发病机制中具有潜在的重要作用。通过视网膜电描记术、裂隙灯生物显微镜和组织学对感染进行评估。注射了两种浓度的细菌(大约10种和1000种细菌)。结果与野生型菌株相比,无论接种量大小,agr-菌株始终导致b波反应的损失较慢。在注射10种微生物的24小时和48小时,AGR组的临床体征较轻。然而,当注射的细菌数量增加到1000个时,观察到更早的临床体征,两组在感染后48小时都表现出最大的细胞和闪光,以及白色的眼底反射。接种36小时后摘除眼球的组织学检查显示,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-菌株的眼睛保持完全正常。当B波反应丧失100%时进行组织学检查,发现两组患者的视网膜改变都无法区分。结论金黄色葡萄球菌产生的毒素加速了视网膜损伤的发生,从而加重了眼内炎的严重程度。因此,在感染过程早期进行毒素靶向治疗可以保护视网膜功能。
PURPOSE To evaluate the contribution of toxins to the severity of Staphylococcus aureus endophthalmitis. METHODS 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. RESULTS 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. CONCLUSIONS 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.