In Silico Virulence Factor Analysis and Drug Target Identification in Pseudomonas Aeruginosa PA7
Divyesh Swaminathan, Lakshmi Sundeep
ABSTRACT
Pseudomonas aeruginosa PA7 is a multidrug-resistant outlier strain with unique virulence factors that contribute to its pathogenicity. Unlike other P. aeruginosa strains, PA7 exhibits resistance to several conventional antibiotics, making treatment options limited. Targeting their unique virulence factors offers a promising alternative therapeutic strategy, as it reduces selective pressure for resistance development.
This study aims to identify PA7-specific virulence factors, functionally annotate them, and screen potential small-molecule inhibitors using an in-silico drug discovery approach. By focusing on virulence rather than viability, the study seeks to explore novel antivirulence strategies against P. aeruginosa PA7.
Unique virulence-associated genes were determined through comparative genomic analysis. Functional annotation was performed using InterProScan and UniProt, followed by human non-homology filtering via BLASTp. The ligand structures were obtained from PubChem and prepared using Open Babel. Protein-ligand docking was performed using AutoDock4, and binding affinity (ΔG) along with inhibition constants (Ki) were analyzed to assess potential drug candidates.
This study successfully identified PA7-specific virulence factors and screened potential inhibitors that could be repurposed as antivirulence therapeutics. The In silico docking results indicate that Triclosan, Salicylidene acylhydrazide, and Patuletin have strong binding affinities, making them promising drug candidates. Further in vitro and in vivo validation is essential to confirm their efficacy in targeting PA7 virulence without inducing resistance. The findings contribute to the growing field of antivirulence therapy and provide a foundation for future drug development against multidrug-resistant P. aeruginosa PA7.
KEYWORDS: Pseudomonas aeruginosa PA7, Virulence factors, In Silico drug discovery, Molecular docking
