Bacteria employ a number of resistance mechanisms against antimicrobials, commonly including target site modification, antimicrobial degradation and active efflux. Of these mechanisms, efflux is unique in that a single efflux system can confer resistance to a remarkably broad range of structurally dissimilar antibiotics and biocides that have different intracellular targets and modes of action. For example, in the opportunistic pathogens Staphylococcus aureus and Acinetobacter baumannii, single multidrug efflux systems facilitate the extrusion of agents as broad and diverse as quaternary ammonium compounds, intercalating dyes, diamidines, biguanidines, anionic detergents, aminoglycosides, ?-lactams, chloramphenicol, tetracyclines, trimethoprim and fluoroquinolones (Table 1). This promiscuity of substrates, coupled with the genetic linkage of exporter genes with other resistance determinants on transferable elements such as plasmids, raises the possibility of cross and co-resistance to biocides and antibiotics. Furthermore, data generated by our and other research groups clearly demonstrate a remarkable propensity of multidrug efflux systems to bind new substrates following only minor amino acid changes to their active sites.
|Number of pages||4|
|Publication status||Published - 2010|