Antiquorum sensing activity of silver nanoparticles in P. aeruginosa: an in silico study

Abstract

Pseudomonas aeruginosa an opportunistic pathogen regulates its virulence through Quorum sensing (QS) mechanism comprising of Las and Rhl system. Targeting of QS mechanism could be an ideal strategy to combat infection caused by P. aeruginosa. Silver nanoparticles (AgNPs) have been broadly applied as antimicrobial agents against a number of pathogenic bacterial and fungal strains, but have not been reported as an anti-QS agent. Therefore, the aim of present work was to show the computational analysis for the interaction of AgNPs with the QS system using an In silico approach. In silico studies showed that AgNPs got 'locked' deeply into the active site of respective proteins with their surrounding residues. The molecular docking analysis clearly demonstrated that AgNPs got bound to the catalytic cleft of LasI synthase (Asp73-Ag = 3.1 Å), RhlI synthase (His52-Ag = 2.8 Å), transcriptional receptor protein LasR (Leu159-Ag = 2.3 Å) and RhlR (Trp10-Ag = 3.1 Å and Glu34-Ag = 3.2 Å). The inhibition of LasI/RhlI synthase by AgNPs blocked the biosynthesis of AHLs, thus no AHL produced, no QS occurred. Further, interference with transcriptional regulatory proteins led to the inactivation of LasR/RhlR system that finally blocked the expression of QS-controlled virulence genes. Our findings clearly demonstrate the anti-QS property of AgNPs in P. aeruginosa which could be an alternative approach to the use of traditional antibiotics for the treatment of P. aeruginosa infection.

Keywords: In silico; Molecular docking; Pseudomonas aeruginosa; Quorum sensing; Silver nanoparticles; Virulence.

Fig. 1

3D structure of Acyl-homoserine lactone (AHL) Synthase LasI (a); binding of AgNPs with the active site of LasI (b); close view of catalytic site of LasI, with bound Ag represented as blue sphere. Amino acids residues (Asp73) of LasI involved in the interaction with AgNPs (c). LasI active site has been depicted by PyMol viewer. Interaction analysis of AgNPs with LasI has been explored through PatchDock

Fig. 2

3D structure of transcriptional activator protein LasR (a); binding of AgNPs with the active site of LasR (b); close view of catalytic site of LasR, with bound Ag represented as blue sphere. Amino acids residues (Leu159) of LasR involved in the interaction with AgNPs (c). LasR active site has been depicted by PyMol viewer. Interaction analysis of AgNPs with LasR has been explored through PatchDock

Fig. 3

3D structure of Acyl-homoserine lactone (AHL) Synthase RhlI (a); RAMPAGE validation of conformation of RhlI (b); binding of AgNPs with the active site of RhlI (c); close view of catalytic site of RhlI, with bound Ag represented as blue sphere. Amino acids residues (His52) of RhlI involved in the interaction with AgNPs (d). RhlI active site has been depicted by PyMol viewer. Interaction analysis of AgNPs with RhlI has been explored through PatchDock

Fig. 4

3D structure of regulatory protein RhlR (a); RAMPAGE validation of conformation of RhlR (b); binding of AgNPs with the active site of RhlR (c); close view of catalytic site of RhlR, with bound Ag represented as blue sphere. Specific residues (i.e., Trp10 & Glu34) of RhlR involved in the interaction with AgNPs (d). RhlR active site has been depicted by PyMol and the interaction analysis of AgNPs with RhlR has been explored by PatchDock

Fig. 5

Schematic representation of anti-QS activity of green synthesized AgNPs