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

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Abstract

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.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We are grateful to She Pengfei (Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University) with providing bacterial strains and technical support.

Funding

The authors are grateful for the funding support by Hunan Provincial Natural Science Foundation of China (Grant No. 2023JJ30060), and the Changsha Science and Technology Bureau Scientific Research Project (Grant No. Kq2004155).

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Authors and Affiliations

  1. Department of Clinical Laboratory, The Fourth Hospital of Changsha, Changsha, 410006, Hunan, China

    Zhengli Hou, Biming Zhang, Zuoxun Xiao, Cheng Peng, Zhengshu Que & Ying Xu

  2. Department of Clinical Laboratory, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, 410006, Hunan, China

    Zhengli Hou

  3. Department of Dermatology, The Fourth Hospital of Changsha, No.70, Lushan Road, Yuelu District, Changsha, 410006, Hunan, China

    Zhiqiang Wu

Authors
  1. Zhengli Hou
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  2. Biming Zhang
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  3. Zuoxun Xiao
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  4. Cheng Peng
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  5. Zhengshu Que
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  6. Ying Xu
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Contributions

Conceptualization: ZH, and ZW; Methodology: ZH, BZ, ZX, CP, and ZQ; Writing Original Draft Preparation: ZH, ZW, and YX; Writing Review and Editing: ZH, and ZW; Supervision: ZW.

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Correspondence to Zhiqiang Wu.

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Hou, Z., Zhang, B., Xiao, Z. et al. Repurposing CD5789 as an Antimicrobial Agent Against MRSA and Its High Resistant Phonotypes. Curr Microbiol 80, 230 (2023). https://doi.org/10.1007/s00284-023-03332-x

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