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Abstract
Multiresistance in Gram-negative pathogens, particularly Pseudomonas aeruginosa, Stenotrophomonas
maltophilia, Acinetobacter spp. and the Enterobacteriaceae, is a significant problem
in medicine today. While multiple mechanisms often contribute to multiresistance,
a broadly distributed family of three-component multidrug efflux systems is an increasingly
recognised determinant of both intrinsic and acquired multiresistance in these organisms.
Homologues of these efflux systems are also readily identifiable in the genome sequences
of a wide range of Gram-negative organisms, pathogens and non-pathogens alike, where
they probably promote efflux-mediated resistance to multiple antimicrobials. Significantly,
these systems often accommodate biocides, raising the spectre of biocide-mediated
selection of multiresistance in Gram-negative pathogens. While there is some debate
as to the natural function of these efflux systems, only some of which are inducible
by their antimicrobial substrates, their contribution to resistance in a variety of
pathogens nonetheless makes them reasonable targets for therapeutic intervention.
Indeed, given the incredible chemical diversity of substrates accommodated by these
efflux systems, it is likely that many novel or yet to be discovered antimicrobials
will themselves be efflux substrates and, as such, efflux inhibitors may become an
important component of Gram-negative antimicrobial therapy.