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GENERAL ARTICLEJ. Ind. Vet. Assoc., Kerala. 10 (1)1. Reversal of acquired antibiotic resistanceconferred by over expression of an EP.2. Removal of intrinsic antibiotic resistancecontributed by EPs3. To reduce the frequency of emergence ofresistant mutant strains.4. For reduction of bacterial virulence in vivo-Recent studies show that S. enterica Subsp.enterica serovar Typhimurium, E. coli, and C.jejuni overexpressing EPs are resistant to highconcentrations of bile salts. In addition, overexpression of EP in N. gonorrhoeae enhancesthe bacterial survival inside host (Piddock,2006). Moreover, outer channel components ofRND EPs are involved in seceretion of bacterialtoxins. Thus EPIs can be used as new weaponagainst secretion of virulence factors and toreduce the bacterial survival in vivo.5. Provide a new method for screening newantibiotics.TARGETS - Inhibition of pump activity may beachieved by different ways.1. Changing the chemical design of previousantibiotics to reduce its affinity for efflux.Tigecycline is a new antibiotic exhibitingreduced affinity for Tet pumps (Someya et al.,1995).2. Repressing the expression of EP genes byaltering its regulatory steps using antisenseoligonucleotides or small interfering RNA. Thispatented strategy was used for the inhibition ofAcrAB EP in E. coli (Van Bambeke et al., 2006).3. Inhibiting the functional assembly of the multicomponentpump- Globomycin can remove thelipoprotein signal sequence of exportedmembrane proteins. Mallea et al. (2002)reported that globomycin at selectedconcentrations restore chloramphenicolintracellular accumulation in MDR E. aerogeneswhich overproduces EP.4. Blocking the outermembrane channel with aplug- Use of nano-antibodies or a moleculeexhibiting strong affinity for the channel areaexposed at the cell-surface may achieve it(Zechini and Versace, 2009). Although this mayyield an efficient EPI, it remains as an attractivehypothesis at this moment.5. By collapsing the energy of efflux- Carbonylcyanide m-chlorophenylhydrazone (CCCP) andpotassium cyanide are used in the laboratory tototally abolish the efflux of drugs (Pages et al.,2005). But it raises the question, whether it istheir direct effect on EP activity or the alterationof cell envelope induces bacterial death.Although no molecule belonging to this categoryhas been currently developed for clinical use orhas been patented, phenothiazines may servethis need in future.6. By creating competitive or non-competitiveinhibition to the affinity sites of EP (Mahamoudet al., 2007).CLASSIFICATION OF EPIs1. ANTIBIOTIC ANALOGUESChemical modification of substrates of EPs byincorporating structural motifs of inhibitors is aninteresting approach for identifying new and potentEPIs. Nelson and Levy (1999) demonstrated theability of 13-cyclopentylthio-tetracycline to inhibitTetB in E. coli. German et al. (2008) showed that acore of ofloxacin conjugated with bisaryl urea is apotent inhibitor of NorA and MepA in S. aureus.2. DRUGS OTHER THAN ANTIBIOTICSDrugs other than antibiotics having EPIactivity are summarized in the Table No.13. NATURAL SOURCESNatural products that have been identified asEPIs are given in the Table 2.4. SYNTHETIC COMPOUNDSDuring this decade, various compounds have70