Virtual screening of plant compounds and nonsteroidal anti-inflammatory drugs for inhibition of quorum sensing and biofilm formation in Salmonella

Abstract

Salmonella belongs to the Enterobacteriaceae family which is widely distributed in the environment due to its adaptive capacity to stress conditions. In addition, Salmonella is able to perform a type of cell-to-cell communication called quorum sensing, which leads to differential gene expression. The quorum sensing system mediated by AI-1, acyl homoserine lactones (AHLs), is incomplete in Salmonella because the luxI homolog gene, which encodes for AI-1 synthase, is missing in the genome. However, a homologue of LuxR, known as SdiA, is present and allows the detection of signaling molecules produced by other species of bacteria, leading to regulation of gene expression, mainly related to virulence and biofilm formation. Thus, in view of the importance of quorum sensing on the physiology regulation of microorganisms, the aim of the present study was to perform a virtual screening of plant compounds and nonsteroidal anti-inflammatory drugs (NASIDs) for inhibition of quorum sensing by molecular docking and biofilm formation in Salmonella. In general, most plant compounds and all NSAIDs bound in, at least, one of the three modeled structures of SdiA proteins of Salmonella Enteritidis PT4 578. In addition, many tested compounds had higher binding affinities than the AHLs and the furanones which are inducers and inhibitors of quorum sensing, respectively. The Z-phytol and lonazolac molecules were good candidates for the in vitro inhibition tests of quorum sensing mediated by AI-1 and biofilm formation in Salmonella. Thus, this study directs future prospecting of plant extracts for inhibition of quorum sensing mechanism depending on AHL and biofilm formation. In addition, the use of inhibitors of quorum sensing and biofilm formation can be combined with antibiotics for better treatment efficacy, as well as the use of these compounds to design new drugs.

Investigating the Mechanism of Action of Diketopiperazines Inhibitors of the Burkholderia cenocepacia Quorum Sensing Synthase CepI: A Site-Directed Mutagenesis Study

“…Quorum sensing inhibitors appear as very promising potentiators of the classical antibiotic therapy to treat dangerous infections such as those caused by B. cenocepacia , for which a lack of new solutions is massively reported ( Horsley et al, 2011 ; Regan and Bhatt, 2016 ; Scoffone et al, 2017 ). Searching in PubMed for “quorum sensing inhibitors” retrieves 51 results in the first 5 months of 2018, which shows the increasing interest in alternative routes to counteract the emergence of resistance among bacteria such as Proteus mirabilis ( Yu et al, 2018 ), Salmonella ( de Almeida et al, 2018 ), Pseudomonas aeruginosa ( Almohaywi et al, 2018 ), Staphylococcus aureus ( Karathanasi et al, 2018 ).…”

Essential Oils and Microbial Communication

“…Different research groups are thus carrying a Essential Oils and Microbial Communication DOI: http://dx.doi.org/10.5772/intechopen.85638 screening of "no-drug compounds," including the EOs, in association with nonsteroidal anti-inflammatory drugs (the so-called NSAIDs) for inhibition of quorum sensing and biofilm formation in pathogens. Some NSAIDs, such as Z-phytol and lonazolac, can block the QS system of Salmonella enteritidis, acting as antagonists with respect to the AHLs [102]. The association of EOs with azolic drugs gives interesting challenges in the treatment of fungal infections determined by fungi particularly difficult to be eradicated [103].…”

Effect of Capsicum Frutescens Extract, Capsaicin, and Luteolin on Quorum Sensing Regulated Phenotypes

“…Docking studies were performed according to Almeida, Pinto, and Vanetti () and Almeida, Vargas, Carneiro, Pinto, and Vanetti (). The crystallized structures of CviR of C. violaceum ATCC 12472 (PDB: 3QP6 and 3QP8; Chen et al., ) with different ligands (C6‐HSL and C10‐HSL) were obtained in the RCSB‐Protein Data Bank database (PDB; http://www.rcsb.org/pdb/home/home.do).…”

“…Lower scores correspond to higher binding affinities. The five best docking scores of each compound were selected for the inspection of the binding sites on the active site of CviR (Almeida, Pinto et al, 2016;Almeida, Vargas et al, 2018).…”