Peran Jacquelyn E, Salvador-Reyes Lilibeth A
Marine Science Institute, College of Science, University of the Philippines Diliman, Quezon City, Philippines.
Front Pharmacol. 2024 May 23;15:1379643. doi: 10.3389/fphar.2024.1379643. eCollection 2024.
New approaches to combating microbial drug resistance are being sought, with the discovery of biofilm inhibitors considered as alternative arsenal for treating infections. Natural products have been at the forefront of antimicrobial discovery and serve as inspiration for the design of new antibiotics. We probed the potency, selectivity, and mechanism of anti-biofilm activity of modified oxylipins inspired by the marine natural product turneroic acid. Structure-activity relationship (SAR) evaluation revealed the importance of the epoxide moiety, regardless of the position, for inhibiting biofilm formation. -12,13-epoxyoctadecanoic acid () and -9,10 epoxyoctadecanoic acid () selectively target the early stage of biofilm formation, with no effect on planktonic cells. These compounds interrupt the formation of a protective polysaccharide barrier by significantly upregulating the operon's transcriptional repressor. This was corroborated by docking experiment with SarA and scanning electron micrographs showing reduced biofilm aggregates and the absence of thread-like structures of extrapolymeric substances. evaluation revealed that and can interfere with the AgrA-mediated communication language in Staphylococci, typical to the diffusible signal factor (DSF) capacity of lipophilic chains.
人们正在寻找对抗微生物耐药性的新方法,生物膜抑制剂的发现被视为治疗感染的替代武器库。天然产物一直处于抗菌药物发现的前沿,并为新型抗生素的设计提供灵感。我们探究了受海洋天然产物特纳罗酸启发的改性氧脂素的抗生物膜活性的效力、选择性和作用机制。构效关系(SAR)评估表明,无论环氧部分位于何处,对于抑制生物膜形成都很重要。-12,13-环氧十八烷酸()和-9,10-环氧十八烷酸()选择性地靶向生物膜形成的早期阶段,对浮游细胞没有影响。这些化合物通过显著上调操纵子的转录阻遏物来中断保护性多糖屏障的形成。这通过与SarA的对接实验以及扫描电子显微镜照片得到证实,照片显示生物膜聚集体减少且不存在胞外聚合物的丝状结构。评估表明,和可以干扰葡萄球菌中AgrA介导的通讯语言,这是亲脂性链的典型可扩散信号因子(DSF)能力。