Secnidazole Is a Promising Imidazole Mitigator of Serratia marcescens Virulence

Serratia marcescens is an opportunistic pathogen that causes diverse nosocomial infections. S. marcescens 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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Serratia marcescens</i> quorum sensing secnidazole anti-virulence agents anti-quorum sensing agents virulence factors Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a697bcb2312c4d3093c460c0c73ff9c3
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spelling	oai:doaj.org-article:a697bcb2312c4d3093c460c0c73ff9c32021-11-25T18:25:12ZSecnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence10.3390/microorganisms91123332076-2607https://doaj.org/article/a697bcb2312c4d3093c460c0c73ff9c32021-11-01T00:00:00Zhttps://www.mdpi.com/2076-2607/9/11/2333https://doaj.org/toc/2076-2607<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>.Ahdab N. KhayyatHisham A. AbbasMaan T. KhayatMoataz A. ShaldamMomen AskouraHani Z. AsfourEl-Sayed KhafagyAmr S. Abu LilaAhmed N. AllamWael A. H. HegazyMDPI AGarticle<i>Serratia marcescens</i>quorum sensingsecnidazoleanti-virulence agentsanti-quorum sensing agentsvirulence factorsBiology (General)QH301-705.5ENMicroorganisms, Vol 9, Iss 2333, p 2333 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Serratia marcescens</i> quorum sensing secnidazole anti-virulence agents anti-quorum sensing agents virulence factors Biology (General) QH301-705.5
spellingShingle	<i>Serratia marcescens</i> quorum sensing secnidazole anti-virulence agents anti-quorum sensing agents virulence factors Biology (General) QH301-705.5 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
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>.
format	article
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
title	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_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_sort	secnidazole is a promising imidazole mitigator of <i>serratia marcescens</i> virulence
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a697bcb2312c4d3093c460c0c73ff9c3
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Secnidazole Is a Promising Imidazole Mitigator of <i>Serratia marcescens</i> Virulence

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