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GENERAL ARTICLEEFFLUX PUMP INHIBITORS FORANTIBACTERIAL THERAPYSumithra T G, Chaturvedi V K, Susan Cherian,Binsila B Krishnan and Siju Susan JacobIndian Veterinary Research Institute, Izatnagar, U.PINTRODUCTIONFor the past seventy years, antibiotics arethe best weapons against bacteria which haveturned bacterial infections from life-threateningsituations into treatable conditions. Butindiscriminate use of antibiotics again changed thescenario by leading to the emergence of multi-drugresistant bacteria. Though this is not a new problem,it is becoming more dangerous these days and canbe best contemplated by news from Science daily(2011) stating that drug resistant bacterialinfections cause more than 25,000 deaths and €1.5billion in extra healthcare costs every year inEuropean Union alone. According to U.S. Centerfor Disease Control and Prevention (CDC, 2010),each year 90,000 people in the United States diebecause of drug-resistant bacteria indicating thenecessity for the discovery of new antibacterialsand resistance-modifying agents. But the pace ofanti-infective research is dramatically slow andonly one new class of antibacterials(oxazolidinones) has reached the market recently(Marquez, et. al., 2005). The rapid emergence ofantibiotic resistant pathogens and slow arrival ofnew antibiotics threatens the present and futuremedical and veterinary science. So novel alternatetherapeutic approaches must be looked upon to facethis threat and one of such option is efflux pumpinhibitors.EFFLUX PUMPSThree main mechanisms are involved inantibiotic resistance which include modification ofthe drug target, enzymatic inactivation of theantibiotics and default of its accumulation withinbacteria due to efflux systems.Efflux is the pumping of a solute out of acell. Efflux pumps (EPs) are membrane-associatedactive transporters promoting the extrusion of toxiccompounds including antibiotics. This decreasestheir intracellular concentration resulting in lesssusceptibility. Simultaneously this predisposes theemergence of higher level adaptive resistancemechanisms, as target mutations (Zechini andVersace, 2009). Mainly there are two types of EPsin bacteria. Those systems which confer resistanceto a specific drug (specific drug resistance (SDR)transporters) or to class of drugs (MDR effluxpumps) (Marquez, 2005). Multi Drug Resistant(MDR) EPs can handle a wide variety ofstructurally unrelated compounds.The microbial drug efflux was firstreported by Ball et al. (1980) and Mc Murry et al.(1980) for tetracycline in E. coli. The multidrugefflux systems have recently been identified assignificant determinants of resistance by Poole(2002). Phylogenetically, bacterial antibiotic EPsbelong to five super families that are classified intwo distinct types as primary transporters (drugextrusion by ATP hydrolysis) and secondarytransporters (by trans-membrane electrochemicalgradients) (Stavri et al., 2007). MDR among Grampositivebacteria is mainly conferred by MFS(major facilitator super family) and that for Gramnegativebacteria is RND (resistance nodulationand cell division) family.EFFLUX PUMPS INHIBITORS (EPIs) -The study of EPs in bacteria shows that itsinhibitors can be used for-JIVA Vol. 10 Issue 1 April 201269