Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence

<i>Serratia marcescens</i> is an opportunistic pathogen that causes diverse nosocomial infections. <i>S. marcescens</i> has developed considerable resistance to different antibiotics and is equipped with an armory of virulence factors. These virulence factors are regulated in...

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Main Authors: Ahdab N. Khayyat, Hisham A. Abbas, Maan T. Khayat, Moataz A. Shaldam, Momen Askoura, Hani Z. Asfour, El-Sayed Khafagy, Amr S. Abu Lila, Ahmed N. Allam, Wael A. H. Hegazy
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/9/11/2333
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author Ahdab N. Khayyat
Hisham A. Abbas
Maan T. Khayat
Moataz A. Shaldam
Momen Askoura
Hani Z. Asfour
El-Sayed Khafagy
Amr S. Abu Lila
Ahmed N. Allam
Wael A. H. Hegazy
author_facet Ahdab N. Khayyat
Hisham A. Abbas
Maan T. Khayat
Moataz A. Shaldam
Momen Askoura
Hani Z. Asfour
El-Sayed Khafagy
Amr S. Abu Lila
Ahmed N. Allam
Wael A. H. Hegazy
author_sort Ahdab N. Khayyat
collection DOAJ
description <i>Serratia marcescens</i> is an opportunistic pathogen that causes diverse nosocomial infections. <i>S. marcescens</i> has developed considerable resistance to different antibiotics and is equipped with an armory of virulence factors. These virulence factors are regulated in <i>S. marcescens</i> by an intercellular communication system termed quorum sensing (QS). Targeting bacterial virulence and QS is an interesting approach to mitigating bacterial pathogenesis and overcoming the development of resistance to antimicrobials. In this study, we aimed to evaluate the anti-virulence activities of secnidazole on a clinical isolate of <i>S. marcescens</i>. The effects of secnidazole at sub-inhibitory concentrations (sub-MICs) on virulence factors, swarming motility, biofilm formation, proteases, hemolysin activity, and prodigiosin production were evaluated in vitro. Secnidazole’s protective activity against <i>S. marcescens</i> pathogenesis was assessed in vivo in mice. Furthermore, a molecular docking study was conducted to evaluate the binding ability of secnidazole to the <i>S. marcescens</i> SmaR QS receptor. Our findings showed that secnidazole at sub-MICs significantly reduced <i>S. marcescens</i> virulence factor production in vitro and diminished its pathogenesis in mice. The <i>insilico</i> docking study revealed a great ability of secnidazole to competitively hinder the binding of the autoinducer to the SmaR QS receptor. In conclusion, secnidazole is a promising anti-virulence agent that may be used to control infections caused by <i>S. marcescens</i>.
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spelling doaj.art-a697bcb2312c4d3093c460c0c73ff9c32023-11-23T00:29:51ZengMDPI AGMicroorganisms2076-26072021-11-01911233310.3390/microorganisms9112333Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> VirulenceAhdab N. Khayyat0Hisham A. Abbas1Maan T. Khayat2Moataz A. Shaldam3Momen Askoura4Hani Z. Asfour5El-Sayed Khafagy6Amr S. Abu Lila7Ahmed N. Allam8Wael A. H. Hegazy9Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh 33511, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt<i>Serratia marcescens</i> is an opportunistic pathogen that causes diverse nosocomial infections. <i>S. marcescens</i> has developed considerable resistance to different antibiotics and is equipped with an armory of virulence factors. These virulence factors are regulated in <i>S. marcescens</i> by an intercellular communication system termed quorum sensing (QS). Targeting bacterial virulence and QS is an interesting approach to mitigating bacterial pathogenesis and overcoming the development of resistance to antimicrobials. In this study, we aimed to evaluate the anti-virulence activities of secnidazole on a clinical isolate of <i>S. marcescens</i>. The effects of secnidazole at sub-inhibitory concentrations (sub-MICs) on virulence factors, swarming motility, biofilm formation, proteases, hemolysin activity, and prodigiosin production were evaluated in vitro. Secnidazole’s protective activity against <i>S. marcescens</i> pathogenesis was assessed in vivo in mice. Furthermore, a molecular docking study was conducted to evaluate the binding ability of secnidazole to the <i>S. marcescens</i> SmaR QS receptor. Our findings showed that secnidazole at sub-MICs significantly reduced <i>S. marcescens</i> virulence factor production in vitro and diminished its pathogenesis in mice. The <i>insilico</i> docking study revealed a great ability of secnidazole to competitively hinder the binding of the autoinducer to the SmaR QS receptor. In conclusion, secnidazole is a promising anti-virulence agent that may be used to control infections caused by <i>S. marcescens</i>.https://www.mdpi.com/2076-2607/9/11/2333<i>Serratia marcescens</i>quorum sensingsecnidazoleanti-virulence agentsanti-quorum sensing agentsvirulence factors
spellingShingle Ahdab N. Khayyat
Hisham A. Abbas
Maan T. Khayat
Moataz A. Shaldam
Momen Askoura
Hani Z. Asfour
El-Sayed Khafagy
Amr S. Abu Lila
Ahmed N. Allam
Wael A. H. Hegazy
Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence
Microorganisms
<i>Serratia marcescens</i>
quorum sensing
secnidazole
anti-virulence agents
anti-quorum sensing agents
virulence factors
title Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence
title_full Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence
title_fullStr Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence
title_full_unstemmed Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence
title_short Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence
title_sort secnidazole is a promising imidazole mitigator of i serratia marcescens i virulence
topic <i>Serratia marcescens</i>
quorum sensing
secnidazole
anti-virulence agents
anti-quorum sensing agents
virulence factors
url https://www.mdpi.com/2076-2607/9/11/2333
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