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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...

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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
Descripción
Sumario: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.