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Repurposing of antidiabetics as Serratia marcescens virulence inhibitors

  • Clinical Microbiology - Research Paper
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A Correction to this article was published on 26 March 2021

This article has been updated

Abstract

Background

Serratia marcescens becomes an apparent nosocomial pathogen and causes a variety of infections. S. marcescens possess various virulence factors that are regulated by intercellular communication system quorum sensing (QS). Targeting bacterial virulence is a proposed strategy to overcome bacterial resistance. Sitagliptin anti-QS activity has been demonstrated previously and we aimed in this study to investigate the effects of antidiabetic drugs vildagliptin and metformin compared to sitagliptin on S. marcescens pathogenesis.

Methods

We assessed the effects of tested drugs in subinhibitory concentrations phenotypically on the virulence factors and genotypically on the virulence encoding genes' expressions. The protection of tested drugs on S. marcescens pathogenesis was performed in vivo. Molecular docking study has been conducted to evaluate the interference capabilities of tested drugs to the SmaR QS receptor.

Results

Vildagliptin reduced the expression of virulence encoding genes but did not show in vitro or in vivo anti-virulence activities. Metformin reduced the expression of virulence encoding genes and inhibited bacterial virulence in vitro but did not show in vivo protection. Sitagliptin significantly inhibited virulence factors in vitro, reduced the expression of virulence factors and protected mice from S. marcescens. Docking study revealed that sitagliptin is more active than metformin and fully binds to SmaR receptor, whereas vildagliptin had single interaction to SmaR.

Conclusion

The downregulation of virulence genes was not enough to show anti-virulence activities. Hindering of QS receptors may play a crucial role in diminishing bacterial virulence.

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Authors and Affiliations

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

    Wael A.H. Hegazy

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Maan T. Khayat & Tarek S. Ibrahim

  3. Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Tarek S. Ibrahim

  4. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

    Tarek S. Ibrahim

  5. Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University, Cairo, Egypt

    Mahmoud Youns

  6. Infection control Unit, Zagazig University Hospitals, Zagazig University, Zagazig, 44519, Egypt

    Rasha Mosbah

  7. Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, AL AHSA, 31982, Kingdom of Saudi Arabia

    Wafaa E. Soliman

  8. Microbiology and Immunology Department, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 35712, Egypt

    Wafaa E. Soliman

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  1. Wael A.H. Hegazy
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Correspondence to Wael A.H. Hegazy.

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This article does not include any studies with human participants. Animal experiments have been approved by Institutional Review Board (ethical committee) at the Faculty of Pharmacy, Zagazig University approved. The procedures were performed in compliance with the ARRIVE guidelines, in agreement with the U.K. Animals (Scientific Procedures) Act, 1986, and related guidelines (ECAHZU, 22 April 2015).

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Hegazy, W.A., Khayat, M.T., Ibrahim, T.S. et al. Repurposing of antidiabetics as Serratia marcescens virulence inhibitors. Braz J Microbiol 52, 627–638 (2021). https://doi.org/10.1007/s42770-021-00465-8

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