RND multidrug efflux pumps: what are they good for?

Abstract

Multidrug efflux pumps are chromosomally encoded genetic elements capable of mediating resistance to toxic compounds in several life forms. In bacteria, these elements are involved in intrinsic and acquired resistance to antibiotics. Unlike other well-known horizontally acquired antibiotic resistance determinants, genes encoding for multidrug efflux pumps belong to the core of bacterial genomes and thus have evolved over millions of years. The selective pressure stemming from the use of antibiotics to treat bacterial infections is relatively recent in evolutionary terms. Therefore, it is unlikely that these elements have evolved in response to antibiotics. In the last years, several studies have identified numerous functions for efflux pumps that go beyond antibiotic extrusion. In this review we present some examples of these functions that range from bacterial interactions with plant or animal hosts, to the detoxification of metabolic intermediates or the maintenance of cellular homeostasis.

Keywords: antibiotic resistance; bacterial homeostasis; bacterial virulence; host/bacteria interactions; multidrug efflux pumps; plant/bacteria interactions; quorum sensing.

FIGURE 1

Structure of an RND efflux pump. The figure shows a scheme of the structure of the E. coli AcrAB-TolC system. As shown, the system is a tripartite complex formed by the inner membrane AcrB protein, the outer membrane protein TolC and the membrane fusion protein AcrA. The activity of the AcrB RND protein is coupled to the proton gradient. It has been shown that these efflux pumps can extrude different compounds form the bacterial cytoplasm and the periplasm. Adapted from Blair and Piddock (2009).

FIGURE 2

Representative examples of transcriptional regulation and genetic organization of RND efflux systems. Local regulators can be either transcriptional activators, such as MexT (a) or transcriptional repressors, such as MexR, MexZ, AcrR, or AcrS (b, c, d, and e). The three structural components may be organized in a single operon, such as in the MexEF-OprN (a) or MexAB-OprM (b) systems; alternatively, a given system may use the OMP from another system, such as in the MexXY system using OprM (c). The OMP component may be located elsewhere in the chromosome, such as TolC (f) and can be used by one or more different systems as in the case of AcrAB (d) and AcrEF (e). MexEF-OprN, MexAB-OprM, and MexXY belong to P. aeruginosa; AcrAB and AcrEF belong to E. coli.