School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, 43600 UKM Bangi, Selangor, Malaysia.
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5120, USA Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124, USA Present address: Department of Infectious Disease, Genentech, Inc., South San Francisco, CA 94080, USA.
Biol Open. 2014 Jun 27;3(7):644-55. doi: 10.1242/bio.20148334.
Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans-S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host.
在对抗抗生素耐药性金黄色葡萄球菌菌株传播的担忧日益加剧的情况下，寻找替代治疗分子变得至关重要。此前，我们利用秀丽隐杆线虫-金黄色葡萄球菌筛选平台，从天然提取物和合成化合物库中鉴定潜在的抗感染药物。从筛选中获得的一个命中物是糯米条叶的水提物 (UE-12)，它在不干扰细菌生长的情况下提高了感染线虫的存活率。在这项研究中，我们使用了荧光转基因报告株，并观察到在存在 UE-12 的情况下，感染线虫中 lys-7 防御基因的抑制表达得到了恢复。对选定的一组 PMK-1 和 DAF-16 调节转录物以及这些途径中的功能丧失突变体进行分析表明，UE-12 的保护作用是通过 p38 MAP 激酶和胰岛素样信号通路介导的。对 UE-12 的一组已知生物活性化合物的进一步分析表明，芹菜素 (C18H16O7) 可能是赋予 UE-12 抗感染特性的候选活性分子。综上所述，这些发现强烈表明，糯米条叶提取物是一种有前途的抗感染药物，通过调节感染宿主的免疫反应，为对抗金黄色葡萄球菌感染提供了生存优势。
