Staphylococcus aureus is an important pathogen causing hospital-acquired infections. Methicillin-resistant S. aureus (MRSA), biofilms, and persisters are highly tolerant to traditional antibiotics and make it difficult to treat. Therefore, new antimicrobial agents are urgently needed to treat hard-to-eradicate diseases caused by this bacterium. In this study, candesartan cilexetil (CC), an angiotensin hypertension drug, had strong antimicrobial activity against S. aureus with minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 8–16 μg/ml and 16–32 μg/ml. CC exhibited limited cytotoxicity and low potential to induce drug resistance. In addition, it showed a synergistic antibacterial effect when combined with gentamicin and tobramycin. The effective concentrations to inhibit MRSA biofilm formation were 16–64 μg/ml, and intractable persisters were killed at 4–8 × MIC. Through the analysis of its mechanism of action, it was evident that the membrane permeability was disrupted as well as the cell structure was damaged. Furthermore, we demonstrated that CC had antibacterial effects in vivo in MRSA-infected murine skin abscess models. In conclusion, these results imply that CC might be a potential antibacterial agent for the treatment of S. aureus-associated infections.

金黄色葡萄球菌是引起医院获得性感染的重要病原体。耐甲氧西林金黄色葡萄球菌(MRSA)、生物膜和持久剂对传统抗生素具有高度耐受性，使其难以治疗。因此，迫切需要新的抗菌剂来治疗由这种细菌引起的难以根除的疾病。在这项研究中，坎地沙坦酯 (CC) 是一种血管紧张素高血压药物，具有很强的抗微生物活性。金黄色葡萄球菌最低抑菌浓度 (MIC) 和最低杀菌浓度 (MBC) 为 8–16 μg/ml 和 16–32 μg/ml。CC 表现出有限的细胞毒性和低诱导耐药性的潜力。此外，与庆大霉素、妥布霉素合用时，表现出协同抗菌作用。抑制 MRSA 生物膜形成的有效浓度为 16-64 μg/ml，顽固的持久性微生物在 4-8 × MIC 下被杀死。通过其作用机制分析，明显破坏了细胞膜通透性，破坏了细胞结构。此外，我们证明了 CC 具有抗菌作用体内在 MRSA 感染的小鼠皮肤脓肿模型中。总之，这些结果意味着 CC 可能是一种潜在的抗菌剂，用于治疗金黄色葡萄球菌- 相关感染。