The host-specific role of a multidrug efflux pump is a novel feature in the rhizobia–legume symbioses. Consistent with the RegSR dependency of bdeAB, a B. japonicum regR mutant was found to have a greater sensitivity against the two tested antibiotics and a symbiotic defect that is most pronounced for soybean. Multidrug resistance (MDR) efflux systems are ubiquitous and important means by which living cells cope with toxic compounds in

their environment (Higgins, 2007; Blair & Piddock, 2009). These efflux systems have been classified into five families, whose members recognize and extrude a battery of structurally dissimilar compounds from the cell (Saier & Paulsen, 2001). Transport systems of the resistance/nodulation/cell division (RND) family are the major cause of antibiotic resistance DAPT chemical structure in clinically relevant Gram-negative bacteria (Piddock, 2006). The well-studied RND-type drug export system of Escherichia coli consists of the AcrB transport Nutlin3a protein, localized in the cytoplasmic membrane, the membrane fusion protein AcrA, and the outer membrane protein TolC (Nikaido & Zgurskaya, 2001). The physiological role of MDR efflux systems is not only restricted to antibiotic resistance, but may also enhance the virulence of animal- and human-pathogenic bacteria (Piddock,

2006; Martinez et al., 2009). Plant roots produce and secrete a large diversity of secondary metabolites into the rhizosphere, several of which possess bioactive potential and play important roles in the interaction of plants with soil microorganisms. For example, phytoalexins form a central component of the plant defense system (Hammerschmidt, 1999; Grayer & Kokubun, 2001), and flavonoids serve as crucial

signaling compounds in the symbiotic interaction between nitrogen-fixing rhizobia and their host plants (Long, 2001; Gibson et al., 2008). In phytopathogenic bacteria, MDR efflux systems were shown to contribute to the successful interaction with host plants. Their loss by mutation compromised the bacteria strongly in virulence and in their capability to extrude antibiotics and phytoalexins (see Martinez et al., 2009, and references enough therein). By contrast, little is known about the role of MDR efflux pumps in rhizobia. Mutants of the bean symbiont Rhizobium etli that lack the RmrAB efflux pump (a member of the major facilitator superfamily) are more sensitive to phytoalexins and are impaired in root-nodule formation (Gonzalez-Pasayo & Martinez-Romero, 2000). In Sinorhizobium meliloti, the NolGHI proteins belonging to the RND-type efflux family are possibly involved in the export of nodulation signals (Saier et al., 1994), although this was disputed more recently (Hernandez-Mendoza et al., 2007).