RND pumps across the genus : AdeIJK is the universal efflux pump.

are generally soil-dwelling organisms that can also cause serious human infections. is one of the most common causative agents of infections and is often multidrug resistant. However, an additional 25 species within the genus have also been associated with infection. encodes six resistance nodulation division (RND) efflux pumps, the most clinically relevant class of efflux pumps for antibiotic export, but the distribution and types of RND efflux pumps across the genus is currently unknown. Sixty-four species making up the genus were searched for RND systems within their genomes. We also developed a novel method using conserved RND residues to predict the total number of RND proteins including currently undescribed RND pump proteins. The total number of RND proteins differed both within a species and across the genus. Species associated with infection tended to encode more pumps. AdeIJK/AdeXYZ was found in all searched species of and through genomic, structural and phenotypic work we show that these genes are actually homologues of the same system. This interpretation is further supported by structural analysis of the potential drug-binding determinants of the associated RND-transporters, which reveal their close similarity to each other, and distinctiveness from other RND-pumps in , such as AdeB. Therefore, we conclude that AdeIJK is the fundamental RND system for species in the genus . AdeIJK can export a broad range of antibiotics and provides crucial functions within the cell, for example lipid modulation of the cell membrane, and therefore it is likely that all require AdeIJK for survival and homeostasis. In contrast, additional RND systems, such as AdeABC and AdeFGH, were only found in a subset of that are associated with infection. By understanding the roles and mechanisms of RND efflux systems in , treatments for infections can avoid efflux-mediated resistance and improve patient outcomes.