Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an 710069, China.
College of Natural Resources and Environment, Northwest A&F University, Yangling 712100, China.
Molecules. 2021 Mar 10;26(6):1497. doi: 10.3390/molecules26061497.
Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against from Chinese herbs and investigated baicalin from as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in was assessed using -based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in , including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of on the mammalian cells and attenuated in vivo pathogenicity in a infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the quinolone signal (PQS) system was found to be required for baicalin's impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating infections.
靶向病原体毒力而非其生存能力的治疗方法为治疗感染性疾病和规避抗生素耐药性提供了一种有前途的替代方案。在这项研究中，我们从中药中寻找针对 的抗毒力化合物，并研究了黄芩素作为一种有效的抗毒力化合物。使用基于 的报告基因和表型测定法评估了黄芩素对 中一系列重要毒力因子的影响。使用遗传方法研究了黄芩素抑制毒力的分子机制。通过体外和体内动物模型评估了黄芩素对 致病性的影响。结果表明，黄芩素减弱了 中的许多重要毒力因子，包括 III 型分泌系统 (T3SS)。黄芩素处理降低了 对哺乳动物细胞的细胞毒性，并减弱了 感染模型中的体内致病性。在大鼠肺部感染模型中，黄芩素显著减轻了肺部病理的严重程度，并加速了肺部细菌清除。发现 中的喹诺酮信号 (PQS) 系统的 PqsR 对于黄芩素对 T3SS 的影响是必需的。这些发现表明，黄芩素是治疗 感染的一种很有前途的治疗候选物。
