Medical Sciences

The salient features of this technology are: 1. Microbial fermentation derived previously uncharacterized efflux pump inhibitors (EPIs), having differential specificities towards Gram-positive (RP2) and Gram-negative (RP1) bacterial efflux pumps. 2. RP1& RP2 potentiates several antibiotics (4 to 64-folds), by inhibiting multiple efflux pumps inE. coliS. aureusrespectively. The potentiation activity was better than PAN and Reserpine. The Antibiotic-EPI combination exhibited bactericidal effect in time-kill kinetics . 4. MPC (Mutation Prevention Concentration) of both the antibiotics was reduced, indicating their clinical significance in limiting the frequency of appearance of resistant mutants. 5. Significantly extended post-antibiotic effects (PAEs) as compared to antibiotics tested alone. 6. Both the EPIs appear to be safe on mammalian cellsand non-hemolytic in nature. 7. Unlike CCCP, RP1 and RP2 neither dissipates proton gradient used by the pump nor abolishes the total ATP pool within bacterial cell. 8. RP1 or RP2 did not seem to block mammalian cell Ca+2 channels, unlike Verapamil. 9. The ability of RP1 and RP2 to reduce the intracellular invasion of E. coliandS. aureusrespectively in J774 macrophage cell lines