PDF(Pubmed)
Abstract：
Multi-drug-resistant Staphylococcus aureus infections necessitate novel antibiotic development. D-3263, a transient receptor potential melastatin member 8 (TRPM8) agonist, has potential antineoplastic properties. Here, we reported the antibacterial and antibiofilm activities of D-3263. Minimum inhibitory concentrations (MICs) against S. aureus, Enterococcus faecalis and E. faecium were ≤ 50 µM. D-3263 exhibited bactericidal effects against clinical methicillin-resistant S. aureus (MRSA) and E. faecalis strains at 4× MIC. Subinhibitory D-3263 concentrations effectively inhibited S. aureus and E. faecalis biofilms, with higher concentrations also clearing mature biofilms. Proteomic analysis revealed differential expression of 29 proteins under 1/2 × MIC D-3263, influencing amino acid biosynthesis and carbohydrate metabolism. Additionally, D-3263 enhanced membrane permeability of S. aureus and E. faecalis. Bacterial membrane phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) dose-dependently increased D-3263 MICs. Overall, our data suggested that D-3263 exhibited potent antibacterial and antibiofilm activities against S. aureus by targeting the cell membrane.
摘要：
多重耐药金黄色葡萄球菌感染需要新型抗生素的开发。D-3263，一种瞬时受体电位美司他丁成员8（TRPM8）激动剂，具有潜在的抗肿瘤特性。这里,我们报道了D-3263的抗菌和抗生物膜活性。对金黄色葡萄球菌的最低抑制浓度（MIC），粪肠球菌和屎肠球菌≤50µM。D-3263在4×MIC时对临床耐甲氧西林金黄色葡萄球菌（MRSA）和粪肠球菌菌株表现出杀菌作用。亚抑制D-3263浓度有效抑制金黄色葡萄球菌和粪肠球菌生物膜，用较高的浓度也清除成熟的生物膜。蛋白质组学分析显示29种蛋白质在1/2×MICD-3263下的差异表达，影响氨基酸的生物合成和碳水化合物的代谢。此外,D-3263增强金黄色葡萄球菌和粪肠球菌的膜通透性。细菌膜磷脂磷脂磷脂酰乙醇胺（PE），磷脂酰甘油（PG），和心磷脂（CL）剂量依赖性增加D-3263MIC。总的来说,我们的数据表明,D-3263通过靶向细胞膜对金黄色葡萄球菌表现出有效的抗菌和抗生物膜活性.
