Changchun University of Chinese Medicine, Changchun 130117, China.
Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China.
J Appl Microbiol. 2024 Sep 2;135(9). doi: 10.1093/jambio/lxae235.
Coagulase (Coa), a crucial virulence factor of Staphylococcus aureus (S. aureus), is considered a vital target for anti-virulence strategies. The research aimed to discover a natural compound capable of inhibiting S. aureus infection by targeting the virulence factor Coa.
The study showed that sinensetin at a concentration of 128 μg mL-1 effectively inhibited both Coa-induced coagulation and biofilm formation in S. aureus. However, western blot results indicated that sinensetin did not impact the expression of Coa protein, suggesting that sinensetin may directly target Coa to counteract the virulence of S. aureus. Thermal shift assay results demonstrated that sinensetin enhanced the thermal stability of Coa, supporting the theory of direct binding. Molecular docking and point mutation experiments identified two key binding sites for sinensetin to Coa as R73A-Coa and R204A-Coa. In vivo studies on mice revealed that sinensetin not only reduced lung tissue damage caused by S. aureus infection, but also decreased inflammatory factors in the lung lavage fluid. Furthermore, combining sinensetin with oxacillin improved the survival rates of the Galleria mellonella and mice.
Sinensetin is a promising natural compound that acts as a direct inhibitor of Coa against S. aureus infections.
凝固酶（Coa）是金黄色葡萄球菌（S. aureus）的关键毒力因子，被认为是抗毒力策略的重要靶标。本研究旨在发现一种能够通过靶向毒力因子 Coa 来抑制金黄色葡萄球菌感染的天然化合物。
研究表明，浓度为 128μg mL-1 的莪术二酮可有效抑制 Coa 诱导的金黄色葡萄球菌凝固和生物膜形成。然而，Western blot 结果表明，莪术二酮并不影响 Coa 蛋白的表达，提示莪术二酮可能直接靶向 Coa 以拮抗金黄色葡萄球菌的毒力。热转移测定结果表明，莪术二酮增强了 Coa 的热稳定性，支持直接结合的理论。分子对接和点突变实验确定了莪术二酮与 Coa 的两个关键结合位点，即 R73A-Coa 和 R204A-Coa。体内小鼠研究表明，莪术二酮不仅减轻了金黄色葡萄球菌感染引起的肺部组织损伤，还降低了肺灌洗液中的炎症因子。此外，莪术二酮与苯唑西林联合使用可提高大蜡螟和小鼠的存活率。
莪术二酮是一种有前途的天然化合物，可作为 Coa 的直接抑制剂，用于治疗金黄色葡萄球菌感染。
