Desouky Said E, Abu-Elghait Mohammed, Fayed Eman A, Selim Samy, Yousuf Basit, Igarashi Yasuhiro, Abdel-Wahab Basel A, Mohammed Alsuhaibani Amnah, Sonomoto Kenji, Nakayama Jiro
Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Cairo 11884, Egypt.
Laboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
Metabolites. 2022 Mar 15;12(3):246. doi: 10.3390/metabo12030246.
Anti-virulence agents are non-bacteriostatic and non-bactericidal emerging therapeutic options which hamper the production of virulence factors in pathogenic flora. In and , regulation of virulence genes' expression occurs through the cyclic peptide-mediated accessory gene regulator () and its ortholog quorum sensing systems, respectively. In the present study, we screened a set of 54 actinomycetales secondary metabolites as novel anti-virulence compounds targeting quorum sensing system of the Gram-positive bacteria. The results indicated that four compounds, Phenalinolactones A-D, BU-4664LMe, 4,5-dehydrogeldamycin, and Questinomycin A, potentially inhibit the quorum sensing system and hemolytic activity of . On the other hand, Decatromicin A and B, Okilactomycin, Rishirilide A, Abyssomicin I, and Rebeccamycin selectively blocked the quorum sensing system and the gelatinase production in at sub-lethal concentrations. Interestingly, Synerazol uniquely showed the capability to inhibit both and quorum sensing systems. Further, in silico molecular docking studies were performed which provided closer insights into the mode of action of these compounds and proposed that the inhibitory activity of these compounds could be attributed to their potential ability to bind to the ATP-active site of AgrA. Taken together, our study highlights the potential of actinomycetales secondary metabolites with diverse structures as anti-virulence quorum sensing inhibitors.
抗毒力因子药物是一类新兴的非抑菌和非杀菌治疗选择，可抑制致病菌群中毒力因子的产生。在[具体文献1]和[具体文献2]中，毒力基因的表达调控分别通过环肽介导的辅助基因调节子（Agr）及其直系同源群体感应系统来实现。在本研究中，我们筛选了一组54种放线菌次生代谢产物，作为针对革兰氏阳性菌群体感应系统的新型抗毒力化合物。结果表明，四种化合物，即苯那内酯A - D、BU - 4664LMe、4,5 - 脱氢格尔德霉素和奎斯替霉素A，可能抑制金黄色葡萄球菌的群体感应系统和溶血活性。另一方面，去卡曲霉素A和B、奥基拉霉素、利氏内酯A、深渊霉素I和瑞贝卡霉素在亚致死浓度下选择性地阻断了金黄色葡萄球菌的群体感应系统和明胶酶的产生。有趣的是，西内唑尔独特地显示出抑制金黄色葡萄球菌和表皮葡萄球菌群体感应系统的能力。此外，进行了计算机模拟分子对接研究，这为这些化合物的作用模式提供了更深入的见解，并提出这些化合物的抑制活性可能归因于它们与AgrA的ATP活性位点结合的潜在能力。综上所述，我们的研究突出了具有不同结构的放线菌次生代谢产物作为抗毒力群体感应抑制剂的潜力。
