In Silico Study of Ayapana Triplinervis Bioactive Compounds Against Quorum-Sensing System of Pseudomonas Aeruginosa

Abstract

Quorum sensing (QS) is the way bacterial cells communicate can trigger or regulate pathogenicity in Pseudomonas aeruginosa. Targeting the quorum sensing system with the help of docking algorithms can reduce the cost and time to screen for potential anti-quorum sensing drugs. Ayapana triplinervis, an ethnobotanical from the Philippines is a potential source of bioactive compounds to inhibit quorum sensing. This study shows potential compounds present in Ayapana triplinervis that could disrupt the quorum sensing system in Pseudomonas aeruginosa with the use of molecular docking simulations. Selection and identification of bioactive compounds found in Ayapana triplinervis was based from previous metabolite screening reports. This study utilizes virtual screening in order to identify which among the compounds to be the potent quorum sensing inhibitor. The molecular structures of the thirty-one identified bioactive compounds were obtained from PubChem (nih.gov) in SDF file. These molecular structures of the compounds from Ayapana triplinervis served as the ligands and docked to the active site of the PqsR, PqsD, and LasR of the Pseudomonas aeruginosa using Autodock Vina algorithms. The bioactive compounds were virtually screened using Autodock Vina to determine the binding affinity of each compounds to the active site of PqsR, PqsD, and LasR. Compounds with a low binding affinity has a potential to be developed as anti-quorum agent to Pseudomonas aeruginosa. Results showed that out of the 31 compounds, caryophyllene, trans-nerolidol, 2-(Isobutyryloxy)-Thymol methyl ether, β-elemene, and cyperadiene have successfully inhibited the PqsR, PqsD, and LasR based from the computed binding affinity. 2- (Isobutyryloxy)-Thymol methyl ether formed hydrogen bond in the active site of all the proteins related governing the quorum sensing process of Pseudomonas aeruginosa, making the compound a candidate drug to disrupt the signaling pathway of the system.

In silico identification of novel PqsD inhibitors: promising molecules for quorum sensing interference in Pseudomonas aeruginosa

“…3,12,14 The use of computer aided drug design tools, namely protein-ligand docking and structured-based virtual screening (VS) 15,16 has been shown to help narrow down the list of compounds to test experimentally, with promising results, 17 particularly regarding molecular docking in the PqsD binding pocket. 18,19 The workflow of the present study is presented in Fig. 3 and has been applied to other projects and other bacterial targets.…”

Targeting Pseudomonas aeruginosa MvfR in the battle against biofilm formation: a multi-level computational approach

“…This approach is very attractive because it prevents the expression of virulence genes without putting selective pressure on bacterial growth, leading to much lower rates of resistance. 4,5 QS is a cell-to-cell communication system that is essential for the transcription and regulation of several virulence genes. 1 P. aeruginosa has four QS systems: Las, Rhl, Pqs and Iqs.…”

“…This approach is very attractive because it prevents the expression of virulence genes without putting selective pressure on bacterial growth, leading to much lower rates of resistance. 4,5…”