Active Export Proteins Mediating Drug Resistance in Staphylococci

Drug resistance mediated by integral membrane transporters is an important mode of cellular resistance to cytotoxic agents across all classes of living organisms. Gram-positive bacteria, such as staphylococcal species, are not encapsulated by a selective outer membrane permeability barrier. Therefore, these organisms often employ integral membrane drug transport systems to maintain cellular concentrations of antimicrobials at subtoxic levels. Staphylococcal species, including the opportunistic human pathogen Staphylococcus aureus, encode a multitude of drug exporters, encompassing transporters from each of the five currently recognized families of bacterial drug resistance transporters. A number of these transporters are chromosomally encoded and allow the host cell to realize clinically significant levels of drug resistance after minor mutations to regulatory regions. Others are plasmid-encoded and can be easily passed between staphylococcal strains and species, or acquired from other Gram-positive genera. In combination, staphylococcal drug transporters potentiate resistance to a vast array of antimicrobial compounds, including macrolide, quinolone, tetracycline and streptogramin antibiotics, as well as a broad range of biocides, such as quaternary ammonium compounds, biguanidines and diamidines. An understanding of the genetic and molecular properties of drug transporters will lead to effective treatments of staphylococcal infections. Here we provide a detailed review of the active drug transporters of the staphylococci.