Network analysis for identifying potential anti-virulence targets through whole transcriptome analysis of Pseudomonas aeruginosa and Staphylococcus aureus exposed to certain anti-pathogenic polyherbal formulations

Abstract Transcriptome of two important pathogens, 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. 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 seems 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. Further validation of the potential targets identified in these pathogens 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.