Antivirulence activities of retinoic acids against Staphylococcus aureus

Frontiers in Microbiology

Microbiology

Jin Yeul Ma¹  Jin-Hyung Lee²  Jintae Lee²  Inji Park²  Yulong Tan³ 

[1] Korea Institute of Oriental Medicine, Daegu, Republic of Korea;School of Chemical Engineering, Yeungnam University, Gyeongsan, Republic of Korea;Special Food Research Institute, Qingdao Agricultural University, Qingdao, China;

关键词: antivirulence;    biofilm;    hemolysis;    retinoic acid;    Staphylococcus aureus;    vitamin A;   

DOI  :  10.3389/fmicb.2023.1224085

 received in 2023-05-17, accepted in 2023-08-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

Multidrug-resistant bacteria such as Staphylococcus aureus constitute a global health problem. Gram-positive S. aureus secretes various toxins associated with its pathogenesis, and its biofilm formation plays an important role in antibiotic tolerance and virulence. Hence, we investigated if the metabolites of vitamin A1 might diminish S. aureus biofilm formation and toxin production. Of the three retinoic acids examined, 13-cis-retinoic acid at 10 μg/mL significantly decreased S. aureus biofilm formation without affecting its planktonic cell growth (MIC >400 μg/mL) and also inhibited biofilm formation by Staphylococcus epidermidis (MIC >400 μg/mL), but less affected biofilm formation by a uropathogenic Escherichia coli strain, a Vibrio strain, or a fungal Candida strain. Notably, 13-cis-retinoic acid and all-trans-retinoic acid significantly inhibited the hemolytic activity and staphyloxanthin production by S. aureus. Furthermore, transcriptional analysis disclosed that 13-cis-retinoic acid repressed the expressions of virulence- and biofilm-related genes, such as the two-component arlRS system, α-hemolysin hla, nuclease (nuc1 and nuc2), and psmα (phenol soluble modulins α) in S. aureus. In addition, plant and nematode toxicity assays showed that 13-cis-retinoic acid was only mildly toxic at concentrations many folds higher than its effective antibiofilm concentrations. These findings suggest that metabolites of vitamin A1, particularly 13-cis-retinoic acid, might be useful for suppressing biofilm formation and the virulence characteristics of S. aureus.

【 授权许可】

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Copyright © 2023 Park, Lee, Ma, Tan and Lee.