Under the Microscope Pumping out biocides – cause for concern ?

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, β-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. Staphylococcus aureus and Acinetobacter baumannii are endemic in hospitals worldwide and reports of communityacquired infections by these pathogens are on the rise. To prevent or limit infections caused by these bacteria, considerable effort has gone into improving practices relating to infection control and prevention within hospitals. One such practice involves the use of chemical biocides including quaternary ammonium compounds (QACs) such as dequalinium chloride, biguanides such as chlorhexidine, and phenylesters such as triclosan, in disinfectants, antiseptics and preservatives4. Active efflux, where a membrane protein transports antimicrobial agents out of the cell to reduce their intracellular concentration, is a primary mechanism of biocide resistance in bacteria. S. aureus and A. baumannii provide excellent examples of Gram-positive and Gram-negative pathogens, respectively, that maintain a multitude of efflux systems in their biocide resistance arsenals. There are five main families of transporters that have been shown to participate in antimicrobial resistance (Figure 1). The systems most extensively studied in S. aureus include a number of major facilitator superfamily (MFS) transporters, as well as members of the small multidrug resistance (SMR), multidrug and toxin extrusion (MATE) and ATP-binding cassette (ABC) superfamilies (Table 1). In contrast, in A. baumannii resistance nodulation division (RND) efflux systems have received considerable Karl A Hassan