Ethyl Gallate: A Potent Inhibitor of MexAB-OprM Efflux Pump in Multidrug-Resistant Pseudomonas aeruginosa

Drug resistance in P. aeruginosa has been mediated by several mechanism, out of them efflux pump mediated resistance is one of the most important mechanisms of drug resistance. MexAB-oprM efflux pump capable of recognizing and expelling a variety of structurally unrelated compounds from the bacterial cell confers resistance to a wide range of antibiotics in P. aeruginosa. The aim of the present study was to screen medicinal plants used in Indian traditional medicine to find some potent compound(s) capable of inhibiting the MexAB-oprM pump in P. aeruginosa and also study the synergistic effect of characterized efflux pump inhibitor(s) with resistant antibiotics in Multi-Drug Resistant (MDR) strains of P.aeruginosa. A total of 100 clinical isolates, four knockouts and one MTCC-741 standard strain of P. aeruginosa were used in this study. All the 100 clinical isolates were processed for antibiotic susceptibility assay and EtBr Agar Cartwheel assay for determination of MDR phenotype. A total of 40 plants were screened for the presence of compounds with efflux pump inhibitory activity. The plants showing EPI activity were further explored for their synergistic effect with three different antibiotics. Ten plant extracts have shown considerable EPI activity and out of the 10 active extracts only one methanolic extract of Terminalia chebula fruits has shown synergistic activity with group A (ciprofloxacin, tetracycline and chloramphenicol). The fractionation and purification of T. chebula fruit extract provided ethyl gallate which have shown synergistic activity along with group A antibiotics as well as significant EPI activity. The results of the present study conclude that ethyl gallate works as a potent EPI against overexpressing MexAB-oprM efflux pump in P. aeruginosa and may be used along with the resistant group A antibiotics against Multi-Drug-Resistant P. aeruginosa.