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The promising anti-virulence activity of candesartan, domperidone, and miconazole on Staphylococcus aureus

  • Bacterial and Fungal Pathogenesis - Research Paper
  • Published:
Brazilian Journal of Microbiology Aims and scope Submit manuscript

Abstract

Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S. aureus strains, there is a need for new drugs discovery. Due to the poor supply of new antimicrobials, targeting virulence of S. aureus may generate weaker selection for resistant strains, anti-virulence agents disarm the pathogen instead of killing it. In this study, the ability of the FDA-approved drugs domperidone, candesartan, and miconazole as inhibitors of S. aureus virulence was investigated. The effect of tested drugs was evaluated against biofilm formation, lipase, protease, hemolysin, and staphyloxanthin production by using phenotypic and genotypic methods. At sub-inhibitory concentrations, candesartan, domperidone, and miconazole showed a significant inhibition of hemolysin (75.8–96%), staphyloxanthin (81.2–85%), lipase (50–65%), protease (40–64%), and biofilm formation (71.4–90%). Domperidone and candesartan have similar activity and were more powerful than miconazole against S. aureus virulence. The hemolysins and lipase inhibition were the greatest under the domperidone effect. Candesartan showed a remarkable reduction in staphyloxanthin production. The highest inhibitory effect of proteolytic activity was obtained with domperidone and candesartan. Biofilm was significantly reduced by miconazole. Expression levels of crtM, sigB, sarA, agrA, hla, fnbA, and icaA genes were significantly reduced under candesartan (68.98–82.7%), domperidone (62.6–77.2%), and miconazole (32.96–52.6%) at sub-MIC concentrations. Candesartan showed the highest inhibition activity against crtM, sigB, sarA, agrA, hla, and icaA expression followed by domperidone then miconazole. Domperidone showed the highest downregulation activity against fnbA gene. In conclusion, candesartan, domperidone, and miconazole could serve as anti-virulence agents for attenuation of S. aureus pathogenicity.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

    Amira M. El-Ganiny, Mona A. El-Sayed & Hisham A. Abbas

  2. Microbiology and Immunology Department, School of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt

    Amany I. Gad

  3. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt

    Moataz A. Shaldam

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M.A.E., A.M.E., and H.A.A. designed the study. A.I.G. conducted the experiments. M.A.S. performed the docking study. A.I.G., H.A.A., and A.M.E. analyzed the results and performed the statistical analysis. A.I.G. wrote the manuscript draft. A.M.E. and H.A.A. revised and edited the manuscript. All the authors approved the final manuscript.

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Correspondence to Amany I. Gad.

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El-Ganiny, A.M., Gad, A.I., El-Sayed, M.A. et al. The promising anti-virulence activity of candesartan, domperidone, and miconazole on Staphylococcus aureus. Braz J Microbiol 53, 1–18 (2022). https://doi.org/10.1007/s42770-021-00655-4

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