Cargando…

In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a major cause of nosocomial infections and is often associated with biofilm-mediated antibiotic resistance. The LasR protein is a key component of the quorum system in P. aeruginosa, allowing it to regulate its biofilm-induced pathogenicity. When the bacterial population re...

Descripción completa

Detalles Bibliográficos
Autores principales: Magri, Meryam, Bouricha, El Mehdi, Hakmi, Mohammed, Jaoudi, Rachid EL, Belyamani, Lahcen, Ibrahimi, Azeddine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664429/
https://www.ncbi.nlm.nih.gov/pubmed/38020496
http://dx.doi.org/10.1177/11779322231212755
_version_ 1785148734394335232
author Magri, Meryam
Bouricha, El Mehdi
Hakmi, Mohammed
Jaoudi, Rachid EL
Belyamani, Lahcen
Ibrahimi, Azeddine
author_facet Magri, Meryam
Bouricha, El Mehdi
Hakmi, Mohammed
Jaoudi, Rachid EL
Belyamani, Lahcen
Ibrahimi, Azeddine
author_sort Magri, Meryam
collection PubMed
description Pseudomonas aeruginosa is a major cause of nosocomial infections and is often associated with biofilm-mediated antibiotic resistance. The LasR protein is a key component of the quorum system in P. aeruginosa, allowing it to regulate its biofilm-induced pathogenicity. When the bacterial population reaches a sufficient density, the accumulation of N-(3-oxododecanoyl) acyl homoserine lactone (3O-C12-HSL) leads to the activation of the LasR receptor, which then acts as a transcriptional activator of target genes involved in biofilm formation and virulence, thereby increasing the bacteria’s antibiotic resistance and enhancing its virulence. In this study, we performed a structure-based virtual screening of a natural food database of 10 997 compounds against the crystal structure of the ligand-binding domain of the LasR receptor (PDB ID: 3IX4). This allowed us to identify four molecules, namely ZINC000001580795, ZINC000014819517, ZINC000014708292, and ZINC000004098719, that exhibited a favorable binding mode and docking scores greater than −13 kcal/mol. Furthermore, the molecular dynamics simulation showed that these four molecules formed stable complexes with LasR during the 150-ns molecular dynamics (MD) simulation, indicating their potential for use as inhibitors of the LasR receptor in P. aeruginosa. However, further experimental validation is needed to confirm their activity.
format Online
Article
Text
id pubmed-10664429
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-106644292023-11-20 In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa Magri, Meryam Bouricha, El Mehdi Hakmi, Mohammed Jaoudi, Rachid EL Belyamani, Lahcen Ibrahimi, Azeddine Bioinform Biol Insights Original Research Article Pseudomonas aeruginosa is a major cause of nosocomial infections and is often associated with biofilm-mediated antibiotic resistance. The LasR protein is a key component of the quorum system in P. aeruginosa, allowing it to regulate its biofilm-induced pathogenicity. When the bacterial population reaches a sufficient density, the accumulation of N-(3-oxododecanoyl) acyl homoserine lactone (3O-C12-HSL) leads to the activation of the LasR receptor, which then acts as a transcriptional activator of target genes involved in biofilm formation and virulence, thereby increasing the bacteria’s antibiotic resistance and enhancing its virulence. In this study, we performed a structure-based virtual screening of a natural food database of 10 997 compounds against the crystal structure of the ligand-binding domain of the LasR receptor (PDB ID: 3IX4). This allowed us to identify four molecules, namely ZINC000001580795, ZINC000014819517, ZINC000014708292, and ZINC000004098719, that exhibited a favorable binding mode and docking scores greater than −13 kcal/mol. Furthermore, the molecular dynamics simulation showed that these four molecules formed stable complexes with LasR during the 150-ns molecular dynamics (MD) simulation, indicating their potential for use as inhibitors of the LasR receptor in P. aeruginosa. However, further experimental validation is needed to confirm their activity. SAGE Publications 2023-11-20 /pmc/articles/PMC10664429/ /pubmed/38020496 http://dx.doi.org/10.1177/11779322231212755 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research Article
Magri, Meryam
Bouricha, El Mehdi
Hakmi, Mohammed
Jaoudi, Rachid EL
Belyamani, Lahcen
Ibrahimi, Azeddine
In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa
title In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa
title_full In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa
title_fullStr In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa
title_full_unstemmed In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa
title_short In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa
title_sort in silico identification of natural food compounds as potential quorum-sensing inhibitors targeting the lasr receptor of pseudomonas aeruginosa
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664429/
https://www.ncbi.nlm.nih.gov/pubmed/38020496
http://dx.doi.org/10.1177/11779322231212755
work_keys_str_mv AT magrimeryam insilicoidentificationofnaturalfoodcompoundsaspotentialquorumsensinginhibitorstargetingthelasrreceptorofpseudomonasaeruginosa
AT bourichaelmehdi insilicoidentificationofnaturalfoodcompoundsaspotentialquorumsensinginhibitorstargetingthelasrreceptorofpseudomonasaeruginosa
AT hakmimohammed insilicoidentificationofnaturalfoodcompoundsaspotentialquorumsensinginhibitorstargetingthelasrreceptorofpseudomonasaeruginosa
AT jaoudirachidel insilicoidentificationofnaturalfoodcompoundsaspotentialquorumsensinginhibitorstargetingthelasrreceptorofpseudomonasaeruginosa
AT belyamanilahcen insilicoidentificationofnaturalfoodcompoundsaspotentialquorumsensinginhibitorstargetingthelasrreceptorofpseudomonasaeruginosa
AT ibrahimiazeddine insilicoidentificationofnaturalfoodcompoundsaspotentialquorumsensinginhibitorstargetingthelasrreceptorofpseudomonasaeruginosa