Bacterial antibiotic efflux systems of medical importance

Multidrug efflux systems endow on bacterial cells the ability to limit the access of antimicrobial agents to their targets. By actively pumping out an tibiotic molecules, these systems prevent the intracellular accumulation ne cessary for antibiotics to exert their lethal activity. Drug efflux appears to be one of the most widespread antibiotic resistance mechanisms among mi croorganisms, since it has been demonstrated to occur in many Gram-positive and Gram-negative bacteria including medically important species like stap hylococci, streptococci, enterobacteria and opportunistic pathogens like Ps eudomonas aeruginosa. Efflux pumps can be specific for only one substrate o r accommodate a more or less wide range of noxious products. Export of stru cturally unrelated compounds confers a multidrug-resistance phenotype on ba cterial cells. Therapeutically critical levels of resistance can be achieve d by overexpression of efflux systems, especially in those species such as P. aeruginosa which possess a low outer membrane permeability. It is suspec ted that the dual physiological function of active efflux systems is both t he secretion of intracellular metabolites and the protection against a vari ety of harmful substances that the microorganism may encounter in its natur al environment.