Novel insights from molecular docking of SdiA from Salmonella Enteritidis and Escherichia coli with quorum sensing and quorum quenching molecules

Abstract

Quorum sensing is a cell-to-cell communication mechanism leading to differential gene expression in response to high population density. The autoinducer-1 (AI-1) type quorum sensing system is incomplete in Escherichia coli and Salmonella due to the lack of the AI-1 synthase (LuxI homolog) responsible for acyl homoserine lactone (AHL) synthesis. However, these bacteria encode the AHL receptor SdiA (a LuxR homolog) leading to gene regulation in response to AI-1 produced by other bacteria. This study aimed to model the SdiA protein of Salmonella enterica serovar Enteritidis PT4 578 based on three crystallized SdiA structures from Enterohemorrhagic E. coli (EHEC) with different ligands. Molecular docking of these predicted structures with AHLs, furanones and 1-octanoyl-rac-glycerol were also performed. The available EHEC SdiA structures provided good prototypes for modeling SdiA from Salmonella. The molecular docking of these proteins showed that residues Y63, W67, Y71, D80 and S134 are common binding sites for different quorum modulating signals, besides being conserved among other LuxR type proteins. We also show that AHLs with twelve carbons presented better binding affinity to SdiA than AHLs with smaller side chains in our docking analysis, regardless of the protein structures used. Interestingly, the conformational changes provided by AHL binding resulted in structural models with increased affinities to brominated furanones. These results suggest that the use of brominated furanones to inhibit phenotypes controlled by quorum sensing in Salmonella and EHEC may present a good strategy since these inhibitors seem to specifically compete with AHLs for binding to SdiA in both pathogens.

Mechanism of agonism and antagonism of the Pseudomonas aeruginosa quorum sensing regulator QscR with non‐native ligands

“…Receptors such as LuxR are nonfunctional dimers that require AHL for DNA binding, whereas MrtR‐type receptors are non‐functional monomers that dimerize to bind DNA. In contrast, SdiA (Yao et al ., ) and others function as monomers in the absence or presence of agonists (Nguyen et al ., ; Almeida et al ., ) and dimerization is thought to be induced by DNA binding. The model for QscR activation resembles that of TraR and LasR, where agonists stabilize QscR to aggregation and proteolysis in the cell and bound AHL stabilizes the protein in vivo and in vitro (Zhu and Winans, ; Oinuma and Greenberg, ; Corral Lugo et al ., ).…”

N-dodecanoyl-homoserine lactone influences the levels of thiol and proteins related to oxidation-reduction process in Salmonella

“…These AIs are able to enter and leave the cell by diffusion or through efflux pumps depending on the type of AHL [ 1 , 25 – 27 ]. The AHL molecules bind to the N-terminal domain of the SdiA protein, altering the binding affinity of its C-terminal domain to the DNA and, consequently, regulating the expression of target genes [ 2 , 28 – 31 ].…”

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).…”