Relationship of plcR-regulated factors to Bacillus endophthalmitis virulence
Relationship of plcR-regulated factors to Bacillus endophthalmitis virulence
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DOI：
10.1128/iai.71.6.3116-3124.2003
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发表时间：
2003-06-01
影响因子：
3.1
通讯作者：
Lereclus, D
中科院分区：
文献类型：
--
作者：
Callegan, MC;Kane, ST;Lereclus, D
芽孢杆菌眼内炎的爆炸性、破坏性过程归因于感染过程中产生的毒素。在这项研究中，我们分析了由全球调节因子plcR控制的毒素在实验性眼内炎芽孢杆菌发病机制中的作用。利用卡那霉素耐药盒aphA3插入灭活plcR，构建了蜡样芽孢杆菌和苏云金芽孢杆菌等基因plcR缺失突变体。将大约100 CFU野生型蜡样芽孢杆菌或苏云金芽孢杆菌或plcr缺陷突变体注入兔眼。每种plcr缺陷突变体引起的眼内炎的进化速度都比每种野生型菌株引起的眼内炎慢得多。由plcr缺陷突变体引起的眼内炎兔子，直到感染后42小时视网膜功能才消失，而野生型感染在18小时内导致视网膜功能完全丧失。plcr缺陷眼内炎的眼内炎性细胞内流和视网膜破坏的严重程度接近野生型感染，但直到感染后36小时才出现。感染plcR突变体的眼睛的大体和组织学检查表明，与野生型感染的眼睛相比，前和后段的变化是沉默的。plcr调节因子的缺失显著减轻了芽孢杆菌眼内炎的严重程度。因此，这些结果表明，plcR可能代表了一个靶点，可以为预防芽孢杆菌眼内炎期间失明设计辅助疗法。
The explosive, destructive course of Bacillus endophthalmitis has been attributed to the production of toxins during infection. In this study we analyzed the contribution of toxins controlled by the global regulator plcR to the pathogenesis of experimental Bacillus endophthalmitis. Isogenic plcR-deficient mutants of Bacillus cereus and Bacillus thuringiensis were constructed by insertional inactivation of plcR by the kanamycin resistance cassette, aphA3. Rabbit eyes were injected intravitreally with approximately 100 CFU of wild-type B. cereus or B. thuringiensis or a plcR-deficient mutant. The evolution of endophthalmitis resulting from each plcR-deficient mutant was considerably slower than that caused by each wild-type strain. Retinal function was not eliminated until 42 h postinfection in rabbits with endophthalmitis caused by the plcR-deficient mutants, whereas wild-type infections resulted in a complete loss of retinal function within 18 h. The intraocular inflammatory cell influx and retinal destruction in plcR-deficient endophthalmitis approached the severity observed in wild-ype infections, but not until 36 h postinfection. Gross and histological examinations of eyes infected with plcR mutants demonstrated that the anterior and posterior segment changes were muted compared to the changes observed in eyes infected with the wild types. The loss of plcR-regulated factors significantly attenuated the severity of Bacillus endophthalmitis. The results therefore suggest that plcR may represent a target for which adjunct therapies could be designed for the prevention of blindness during Bacillus endophthalmitis.