Repurposing CD5789 as an Antimicrobial Agent Against MRSA and Its High Resistant Phonotypes

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.