Xu Lanlan, She Pengfei, Chen Lihua, Li Shijia, Zhou Linying, Hussain Zubair, Liu Yaqian, Wu Yong
Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Microbiol. 2021 Sep 13;12:688772. doi: 10.3389/fmicb.2021.688772. eCollection 2021.
is an important pathogen causing hospital-acquired infections. Methicillin-resistant (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 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 MRSA-infected murine skin abscess models. In conclusion, these results imply that CC might be a potential antibacterial agent for the treatment of -associated infections.
是引起医院获得性感染的重要病原体。耐甲氧西林（MRSA）、生物膜和持留菌对传统抗生素具有高度耐受性，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。在本研究中，血管紧张素高血压药物坎地沙坦酯（CC）对其具有强大的抗菌活性，最低抑菌浓度（MICs）和最低杀菌浓度（MBCs）分别为8-16μg/ml和16-32μg/ml。CC表现出有限的细胞毒性和较低的诱导耐药性潜力。此外，它与庆大霉素和妥布霉素联合使用时显示出协同抗菌作用。抑制MRSA生物膜形成的有效浓度为16-64μg/ml，4-8×MIC可杀死难治性持留菌。通过对其作用机制的分析，明显发现膜通透性被破坏以及细胞结构受损。此外，我们证明CC在MRSA感染的小鼠皮肤脓肿模型中具有抗菌作用。总之，这些结果表明CC可能是治疗相关感染的潜在抗菌剂。
