Enterococcus faecalis infections pose a significant clinical challenge due to their multidrug resistance and propensity for biofilm formation. Exploring alternative treatment options, such as repurposing existing drugs, is crucial in addressing this issue. This study investigates the antibacterial activity of candesartan cilexetil against E. faecalis and elucidates its mechanism of action. Candesartan cilexetil exhibited notable antibacterial activity against both E. faecalis and Enterococcus faecium, with minimum inhibitory concentration (MIC) of ≤25 μM. Time-kill curves demonstrated concentration-dependent bactericidal effects. Candesartan cilexetil could significantly inhibited biofilm formation at the concentration of 1/4× MIC and induced alterations in biofilm structure. Permeability assays revealed compromised bacterial membranes, accompanied by the dissipation of membrane potential in E. faecalis cells after treatment with candesartan cilexetil. Checkerboard analysis showed that bacterial membrane phospholipids phosphatidylglycerol and cardiolipin could neutralize the antibacterial activity of candesartan cilexetil in a dose-dependent manner. Biolayer interferometry (BLI) assay indicated specific interactions between candesartan cilexetil and phosphatidylglycerol or cardiolipin. This study demonstrates the promising antibacterial and antibiofilm activities of candesartan cilexetil against multidrug-resistant E. faecalis. The mechanism of action involves disruption of bacterial membranes, possibly by interacting with membrane phospholipids. These findings underscore the potential utility of candesartan cilexetil as an effective therapeutic agent for combating E. faecalis infections, offering a valuable strategy in the battle against antibiotic-resistant pathogens.

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坎地沙坦酯对粪肠球菌的抗菌活性及机制


粪肠球菌感染由于其多重耐药性和生物膜形成倾向而带来重大的临床挑战。探索替代治疗方案，例如重新利用现有药物，对于解决这一问题至关重要。本研究探讨坎地沙坦西酯对粪肠球菌的抗菌活性并阐明其作用机制。坎地沙坦酯对粪肠球菌和屎肠球菌均表现出显着的抗菌活性，最低抑菌浓度（MIC）≤25 μM。时间-杀菌曲线显示了浓度依赖性的杀菌效果。坎地沙坦酯在1/4×MIC浓度下可显着抑制生物膜形成并诱导生物膜结构改变。渗透性测定显示，在用坎地沙坦西酯处理后，粪肠球菌细胞中细菌膜受损，并伴有膜电位耗散。棋盘分析表明，细菌膜磷脂磷脂酰甘油和心磷脂能够以剂量依赖性方式中和坎地沙坦西酯的抗菌活性。生物层干涉测量 (BLI) 测定表明坎地沙坦西酯与磷脂酰甘油或心磷脂之间存在特异性相互作用。这项研究证明坎地沙坦西酯对多重耐药粪肠球菌具有良好的抗菌和抗生物膜活性。作用机制涉及破坏细菌膜，可能是通过与膜磷脂相互作用。这些发现强调了坎地沙坦西酯作为对抗粪肠球菌感染的有效治疗剂的潜在用途，为对抗抗生素耐药病原体提供了有价值的策略。