Zeng Hong, He Qiu-Ying, Yang Sheng-Qiang, Wei Xiao-Lian, Luo Jia-Zi, Zhou Jing-Kai, Fu Rong-Bing, Teng Li-Ping, Zhou Zhong-Bo
Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, 533000, People's Republic of China.
Guangxi Zhuang Autonomous Region Engineering Research Center of Clinical Prevention and Control Technology and Leading Drug for Microorganisms with Drug Resistance in Border Ethnic Areas, Baise, 533000, People's Republic of China.
Curr Microbiol. 2025 Aug 4;82(9):432. doi: 10.1007/s00284-025-04427-3.
In recent years, bacterial drug resistance has increased alarmingly. The scarcity of novel antibiotics and few available drug targets significantly contribute to rising drug resistance. Searching quorum-sensing interfering agents and biofilm formation inhibitors are the most promising approaches for fighting multi-drug resistant bacterial infections. Chinese herbal medicines represent a rich repository for discovering quorum sensing (QS) inhibitors. In a continuation of the search for QS inhibitors from plants of Hypericum, significant bioactivity was observed in the ethyl acetate extract of Hypericum curvisepalum. Twelve known xanthones were obtained from this extract through bioassay-guided fractionation and subsequent identification (1-12), together with an undescribed analogue (16), two chromone derivatives (13 and 14), and a flavonoid (15). Compounds 2, 3, 6, and 7 showed apparent anti-quorum sensing activity against Chromobacterium violaceum ATCC12472 with violacein inhibition rates of 91.2, 90.6, 88.3, and 83.0% at 250 μM. In addition, compounds 2, 3, 6, and 7 also suppressed the motility and significantly reduced the biofilm formation of C. violaceum ATCC12472. Molecular docking analyses, Isothermal titration calorimetry (ITC) and qRT-PCR experiments suggested that these four compounds could bind with CviR receptor and downregulated genes vioB, vioC, and vioD encoding to regulate violacein biosynthesis. Xanthones from Hypericum could be considered as an important source of natural QS inhibitors towards C. violaceum ATCC12472.
近年来，细菌耐药性急剧增加。新型抗生素的稀缺以及可用药物靶点的匮乏极大地促成了耐药性的上升。寻找群体感应干扰剂和生物膜形成抑制剂是对抗多重耐药细菌感染最有前景的方法。中草药是发现群体感应（QS）抑制剂的丰富宝库。在从金丝桃属植物中持续寻找QS抑制剂的过程中，弯萼金丝桃的乙酸乙酯提取物表现出显著的生物活性。通过生物测定导向的分离和后续鉴定，从该提取物中获得了12种已知的呫吨酮（1 - 12），以及一种未描述的类似物（16）、两种色酮衍生物（13和14）和一种黄酮类化合物（15）。化合物2、3、6和7对紫色色杆菌ATCC12472表现出明显的抗群体感应活性，在250μM时对紫菌素的抑制率分别为91.2%、90.6%、88.3%和83.0%。此外，化合物2、3、6和7还抑制了紫色色杆菌ATCC12472的运动性，并显著减少了其生物膜的形成。分子对接分析、等温滴定量热法（ITC）和qRT - PCR实验表明，这四种化合物可与CviR受体结合，并下调编码紫菌素生物合成的vioB、vioC和vioD基因。金丝桃属植物中的呫吨酮可被视为针对紫色色杆菌ATCC12472的天然QS抑制剂的重要来源。
