Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
FEMS Microbiol Lett. 2011 Nov;324(2):147-55. doi: 10.1111/j.1574-6968.2011.02397.x. Epub 2011 Sep 15.
Staphylococcus aureus is a versatile pathogen that can cause life-threatening infections. The growing emergence of methicillin-resistant S. aureus strains and a decrease in the discovery of new antibiotics warrant the search for new therapeutic targets to combat infections. Staphylococcus aureus produces many extracellular virulence factors that contribute to its pathogenicity. Therefore, targeting bacterial virulence as an alternative strategy to the development of new antimicrobials has gained great interest. α-Toxin is a 33.2-kDa, water-soluble, pore-forming toxin that is secreted by most S. aureus strains. α-Toxin is essential for the pathogenesis of pneumonia, as strains lacking α-toxin display a profound defect in virulence. In this report, we demonstrate that isoalantolactone (IAL), a naturally occurring compound found in Inula helenium (Compositae), has no anti-S. aureus activity as per MIC evaluation in vitro. However, IAL can markedly inhibit the expression of α-toxin in S. aureus at very low concentrations. Furthermore, the in vivo data indicate that treatment with IAL protects mice from S. aureus pneumonia.
金黄色葡萄球菌是一种多功能病原体，可导致危及生命的感染。耐甲氧西林金黄色葡萄球菌菌株的不断出现和新抗生素的发现减少，都需要寻找新的治疗靶点来对抗感染。金黄色葡萄球菌产生许多有助于其致病性的细胞外毒力因子。因此，将细菌毒力作为开发新抗菌药物的替代策略引起了极大的兴趣。α-毒素是一种 33.2kDa 的水溶性成孔毒素，由大多数金黄色葡萄球菌菌株分泌。α-毒素对肺炎的发病机制至关重要，因为缺乏α-毒素的菌株在毒力方面存在严重缺陷。在本报告中，我们证明了异土木香内酯（IAL），一种在土木香（菊科）中发现的天然存在的化合物，根据体外 MIC 评估，IAL 没有抗金黄色葡萄球菌活性。然而，IAL 可以在非常低的浓度下显著抑制金黄色葡萄球菌中α-毒素的表达。此外，体内数据表明，IAL 治疗可保护小鼠免受金黄色葡萄球菌肺炎的侵害。
