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.
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.
P. aeruginosa is a notorious pathogen. A multi-drug resistant strain of this bacterium was challenged with a colloidal nano-silver formulation- Silversol. Its minimum inhibitory concentration against P. aeruginosa was found to be 1.5 ppm, and at sub-MIC of 1 ppm, it was able to alter quorum-sensing regulated pigmentation, exopolysaccharide synthesis and biofilm formation, antibiotic susceptibility, protein synthesis and export, nitrogen metabolism, and siderophore production in this pathogen. Transcriptome analysis of the silver-exposed P. aeruginosa indicated generation of nitrosative stress and disturbance of iron homeostasis to be the major mechanisms associated with anti-Pseudomonas activity of Silversol. Network analysis of the differentially expressed genes in silver-treated bacterium identified ten genes as the potential molecular targets: norB, norD, nirS, nirF, nirM, nirQ, nosZ, nosY, narK1, and norE (all associated with nitrogen metabolism or denitrification). Three of them (norB, narK1, and norE) were also validated through RT-PCR.
We investigated anti-pathogenic activity of a polyherbal formulation (Enteropan®) against a multidrugresistant strain of Pseudomonas aeruginosa, wherein the nematode worm Caenorhabditis elegans wasemployed as a model host for the bacterial pathogen.
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