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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-11-01
|
Series: | Microorganisms |
Subjects: | |
Online Access: | https://www.mdpi.com/2076-2607/9/11/2333 |
_version_ | 1827675953328816128 |
---|---|
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>. |
first_indexed | 2024-03-10T05:14:59Z |
format | Article |
id | doaj.art-a697bcb2312c4d3093c460c0c73ff9c3 |
institution | Directory Open Access Journal |
issn | 2076-2607 |
language | English |
last_indexed | 2024-03-10T05:14:59Z |
publishDate | 2021-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Microorganisms |
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 |
work_keys_str_mv | AT ahdabnkhayyat secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT hishamaabbas secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT maantkhayat secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT moatazashaldam secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT momenaskoura secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT hanizasfour secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT elsayedkhafagy secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT amrsabulila secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT ahmednallam secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence AT waelahhegazy secnidazoleisapromisingimidazolemitigatorofiserratiamarcescensivirulence |