Computational Studies Provide a Molecular Basis for the Quorum Sensing Inhibitory Action of Compounds from Dioon spinulosum Dyer Ex Eichler

Abstract

In Pseudomonas aeruginosa, quorum sensing (QS) plays a key role in biofilm formation and the regulation of other virulence factors which make the bacterium resistant to antibacterial action. During QS, LasR is critical for transcriptional activation and virulence gene regulation. In this study, 21 compounds identified in the anti‐quorum sensing and antibiofilm extracts of Dioon spinolosum were screened against LasR using molecular docking and molecular dynamics (MD) simulations. From molecular docking, 8 compounds had docking scores better than the natural autoinducer molecule, and were therefore subjected to molecular dynamics simulations. MD analysis revealed that the compounds bound strongly to LasR while exposing the binding pocket to bulk solvent. This potentially leads to protein aggregation and prevention of LasR dimerization. Hence, this study provides molecular basis for the anti‐quorum sensing and antibiofilm activities of compounds isolated from Dioon spinulosum and thus, can be considered for antibiotics development.

Peptide Extract from Red Kidney Beans, Phaseolus vulgaris (Fabaceae), Shows Promising Antimicrobial, Antibiofilm, and Quorum Sensing Inhibitory Effects

“…Such peptides have a strong affinity for the lipopolysaccharide groups that are the major components of bacterial cell membrane, and this leads to pore formation within the membrane, ultimately exposing intracellular organelles into the extracellular environment. On the other hand, biofilm inhibition is caused by the crude extract binding to the receptors responsible for biofilm formation, such as PqsR and RhlR [ 9 , 26 ]. Pyoverdine, a fundamental siderophore produced by P. aeruginosa , serves the dual function of sequestering iron from host depots and acting as a QS signaling molecule.…”

“…Two additional QS systems, namely, Pseudomonas quinolone signal (PQS) and integrated quorum system (IQS), exist, with the latter's specifics yet to be fully elucidated [ 8 ]. The Las system emerges as a central player in QS, with LasR orchestrating various systems and genes critical for the bacterium's behavior [ 9 ].…”

De novo peptides as potential antimicrobial agents

“…The energy and pressure of the simulations were checked. The root mean square deviations (RMSD), root mean square fluctuations (RMSF) and radius of gyration (Rgyr) were computed using standard GROMACS commands [ 27 , 28 ], and a Ramachandran plot showing Φ and Ψ angles for all residues and snapshots for the peptides were generated. The solvent-accessible surface area (SASA) was calculated by first defining the radius of a probe sphere, which is usually the van der Waals (vdW) radius of water which is rolled along the surface of the selected groups.…”