Department of Clinical Laboratory, The Fourth Hospital of Changsha, Changsha, 410006, Hunan, China.
Department of Clinical Laboratory, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, 410006, Hunan, China.
Curr Microbiol. 2023 May 31;80(7):230. doi: 10.1007/s00284-023-03332-x.
Methicillin-resistant Staphylococcus aureus (MRSA) poses a great threat to human health, and the formation of biofilm and persister cells make the situation even worse. Drug repurposing is an effective way to solve this problem by shortening the drug development times and reducing the research costs. In this study, CD5789 (trifarotene), a fourth-generation retinoid to be approved by the FDA in 2019 for the topical acne vulgaris regimens, was exhibited antimicrobial activity against MRSA type strains and its clinical isolates with the minimal concentration (MIC) of 2-4 μg/mL and 4-16 μg/mL, respectively, in a dose-dependent manner. By crystal violet staining, we found that CD5789 could inhibit the biofilm formation by MRSA and could further eradicate the pre-formed biofilm at the concentration of 8 μg/mL. By checkerboard dilution assay, sub-MIC of CD5789 showed synergistic antimicrobial effects with sub-MIC of gentamycin against MRSA type strains as well as clinical isolates. In addition, CD5789 also exhibited effective bactericidal activity against MRSA persister cells at the concentration of 8 ~ 16 μg/mL. Extremely low cytotoxicity of CD5789 was observed by CCK-8 assay indicated the well tolerability to human body. In all, CD5789 has the potential to be an alternative for the treatment of refractory MRSA-related infections.
耐甲氧西林金黄色葡萄球菌（MRSA）对人类健康构成了巨大威胁，而生物膜的形成和持续存在的细胞使情况更加恶化。药物再利用是解决这一问题的有效方法，可以缩短药物开发时间，降低研究成本。在这项研究中，CD5789（三法罗特），一种将于 2019 年由 FDA 批准用于局部痤疮治疗方案的第四代维甲酸，表现出对 MRSA 标准株及其临床分离株的抗菌活性，其最小浓度（MIC）分别为 2-4μg/mL 和 4-16μg/mL，呈剂量依赖性。通过结晶紫染色，我们发现 CD5789 可以抑制 MRSA 的生物膜形成，并可以在 8μg/mL 的浓度下进一步清除已形成的生物膜。通过棋盘稀释试验，CD5789 的亚 MIC 与庆大霉素的亚 MIC 联合使用对 MRSA 标准株和临床分离株均表现出协同抗菌作用。此外，CD5789 对 MRSA 持续存在的细胞也表现出有效的杀菌活性，浓度为 8~16μg/mL。CCK-8 试验观察到 CD5789 的极低细胞毒性表明其对人体具有良好的耐受性。总之，CD5789 有可能成为治疗难治性 MRSA 相关感染的替代药物。
