Deciphering the molecular mechanisms underlying anti-pathogenic potential of a polyherbal formulation Enteropan against multi-drug resistant Pseudomonas aeruginosa

Anti-pathogenic potential of a polyherbal formulation Enteropan(R) was investigated against a multidrug resistant strain of the bacterium Pseudomonas aeruginosa. Enteropan-pre-exposed P. aeruginosa displayed reduced ([~]70%{downarrow}) virulence towards the model host Caenorhabditis elegans. Enteropan affected various traits like biofilm formation, protein synthesis and secretion, quorum-modulated pigment production, antibiotic susceptibility, nitrogen metabolism etc. in this pathogen. P. aeruginosa could not develop complete resistance to the virulence-attenuating activity of Enteropan even after repeated exposure to this polyherbal formulation. Whole transcriptome analysis showed 17% of P. aeruginosa genome to get differentially expressed under influence of Enteropan. Major mechanisms through which Enteropan exerted its anti-virulence activity were found to be generation of nitrosative stress, oxidative stress, envelop stress, quorum modulation, disturbance of protein homeostasis and metal homeostasis. Network analysis of the differently expressed genes resulted in identification of 10 proteins with high network centrality as potential targets from among the down-regulated genes. Differential expression of genes coding for five (rpoA, tig, rpsB, rpsL, and rpsJ) of these targets was validated through RT-PCR too, and they can further be pursued as potential targets by various drug discovery programmes.