ROLE OF A NOVEL TERPENOID AS EFFLUX INHIBITOR IN TARGETING THE EFFLUX PROTEIN (MexA) OF MULTI-DRUG RESISTANT PSEUDOMONAS AERUGINOSA

Pseudomonas aeruginosa, is one among the few drug resistant organisms causing Urinary Tract Infection. Most strains of Pseudomonas aeruginosa are significantly more resistant, even in the absence of R plasmids, to many antimicrobial agents, including β-lactams, tetracycline, chloramphenicol, and fluoroquinolones, than most other gram-negative rods. This broad-range resistance has so far been assumed to be mainly due to the low permeability of the P. aeruginosa outer membrane. Mex-proteins are the multidrug exporter proteins that are significant in drug ejection, which is the main reason for drug resistance. This limits the therapeutic options. Inhibition of multi drug resistant efflux pumps can restore the activities of antimicrobial agents that are substrates for these proteins. Hence efforts are now taken to screen few medicinal plants, which are both economic and less toxic. Among the several plants screened, we have chosen the acetone extract of Elephantopus scaber from which we purified a new terpenoid for our study. Its structure was generated using CHEMSKETCH software. The novel terpenoid was evaluated as potent efflux inhibitor. In this present study the Mex A protein and terpenoid were docked using Auto dock software and the docking score with minimum binding energy value of -6.82kcal/mol was calculated. It infers that the terpenoid can inhibit the activity of Mex A by forming a strong atomic interaction with the active site residues. Hence the terpenoid can act as a drug for bacterial infections. This study on inhibition of efflux pump using terpenoid would be an alternate but effective solution to combat drug resistant Pseudomonas infections without side effects