EFFLUX PUMPS: AN OVERVIEWAbstract
Antibiotic efflux pumps appear a major component of microbial resistance to many classes of major antibiotics namely the tetracycline, the macrolides, and the fluoroquinolones. These are totally synthetic, amphiphilic compounds with no known ‘natural’ counterpart, antibiotic efflux appears sufficient per se to confer a medium or high level of resistance, defeating medically applicable treatments of the corresponding infections with these antibiotics. Antibiotic efflux may be found in association with other mechanisms, such as antibiotic inactivation, to confer high-level resistance on bacteria. In some respects, this phenomenon bears similarities with the cooperation of drug-extruding pumps and the cytochrome P450-based degradation pathways in enterocytes. An increasing knowledge about a variety of efflux pumps that are involved in MDR of pathogens, is an important challenge for current medicinal chemistry. The existence of antibiotic efflux pumps, and their impact on therapy, must now be taken fully into account for the selection of novel antimicrobials. The design of specific, potent inhibitors appears to be an important goal for the improved control of infectious diseases in the near future. Clinical statistics reveal significant prevalence of antibiotic efflux pumps on resistance with that of the other resistance mechanisms. Recent surveys point to alarming figures of 40 – 90% of some bacterial pathogens (S.pneumonia, S. pyogenes, and P. aeruginosa) bearing efflux mechanisms for the major classes of clinically available antibiotics. An increasing number of patents indicates the intense role of efflux pumps in field of microbiology. Patent searches carried out on various online databases concluded the latest perspectives of efflux pump inhibitors.