[Accepted, unedited version] Network analysis for identifying potential anti-virulence targets from whole transcriptome of Pseudomonas aeruginosa and Staphylococcus aureus exposed to certain anti-pathogenic polyherbal formulations

Abstract

Introduction: Antimicrobial Resistance (AMR) is a serious global threat. Identification of novel antibacterial targets is urgently warranted to help the antimicrobial drug discovery programmes. This study attempted identification of potential targets in two important pathogens Pseudomonas aeruginosa and Staphylococcus aureus. Methods: Transcriptome of Pseudomonas aeruginosa and Staphylococcus aureus exposed to two different quorum-modulatory polyherbal formulations were subjected to network analysis to identify the most highly networked differentially expressed genes (hubs) as potential anti-virulence targets. Results: Genes associated with denitrification and sulfur metabolism emerged as the most important targets in P. aeruginosa. Increased build-up of nitrite (NO2) in P. aeruginosa culture exposed to the polyherbal formulation Panchvalkal was confirmed through in vitro assay too. Generation of nitrosative stress and inducing sulfur starvation seemed to be effective anti-pathogenic strategies against this notorious gram-negative pathogen. Important targets identified in S. aureus were the transcriptional regulator sarA, immunoglobulin-binding protein Sbi, serine protease SplA, the saeR/S response regulator system, and gamma-haemolysin components hlgB and hlgC. Conclusion: Further validation of the potential targets identified in this study is warranted through appropriate in vitro and in vivo assays in model hosts. Such validated targets can prove vital to many antibacterial drug discovery programmes globally.