Programa de Pós-graduação Em Biotecnologia, Universidade Estadual de Feira de Santana, Bahia, Brazil.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
Microb Pathog. 2020 Jul;144:104142. doi: 10.1016/j.micpath.2020.104142. Epub 2020 Mar 13.
Although bacterial resistance is a worldwide growing concern, the development of bacteriostatic and bactericidal drugs has been decreasing in the last decade. Compounds that modulate the microorganism virulence, without killing it, have been considered promising alternatives to combat bacterial infections. However, most signaling pathways that regulate virulence are complex and not completely understood. The rich chemical diversity of natural products offers a good starting point to identify key compounds that shed some light on this matter. Therefore, we investigated the role of Marcetia latifolia ethanolic extract, as well as its major constituent, calycopterin (5,4'-dihydroxy-3,6,7,8-tetramethoxylflavone), in the regulation of virulence-related phenotypes of Pseudomonas aeruginosa. Our results show that calycopterin inhibits pyocyanin production (EC50 = 32 μM), reduces motility and increases biofilm formation in a dose-dependent manner. Such biological profile suggests that calycopterin modulates targets that may act upstream the quorum sensing regulators and points to its utility as a chemical probe to further investigate P. aeruginosa transition from planktonic to sessile lifestyle.
虽然细菌耐药性是一个全球性的问题，但在过去十年中，抑菌和杀菌药物的研发一直在减少。调节微生物毒力而不杀死它的化合物已被认为是对抗细菌感染的有前途的替代品。然而，调节毒力的大多数信号通路都很复杂，尚未完全了解。天然产物丰富的化学多样性为识别关键化合物提供了一个很好的起点，这些化合物可以阐明这一问题。因此，我们研究了 Marcetia latifolia 乙醇提取物及其主要成分飞燕草素（5,4'-二羟基-3,6,7,8-四甲氧基黄酮）在调节铜绿假单胞菌毒力相关表型中的作用。我们的结果表明，飞燕草素以剂量依赖的方式抑制绿脓菌素的产生（EC50=32 μM），降低运动性并增加生物膜形成。这种生物学特征表明，飞燕草素调节的靶标可能作用于群体感应调节剂的上游，表明其可用作化学探针，以进一步研究铜绿假单胞菌从浮游生物到定殖生活方式的转变。
