Efflux Pumps in Species Increase Antibiotic Resistance and Promote Survival in a Coculture Competition Model.

Members of the genus include opportunistic but often-fatal pathogens and soil saprophytes with highly versatile metabolic capabilities. In previous studies of (formerly ) strain CV017, we identified a resistance nodulation division (RND)-family efflux pump (CdeAB-OprM) that confers resistance to several antibiotics, including the bactobolin antibiotic produced by the soil saprophyte Here, we show the genes increase survival in a laboratory competition model with We also demonstrate that adding sublethal bactobolin concentrations to the coculture increases survival, but this effect is not through CdeAB-OprM. Instead, the increased survival requires a second, previously unreported pump we call CseAB-OprN. We show that in cells exposed to sublethal bactobolin concentrations, the genes are transcriptionally induced, and this corresponds to an increase in bactobolin resistance. Induction of this pump is highly specific and sensitive to bactobolin, while CdeAB-OprM appears to have a broader range of antibiotic recognition. We examine the distribution of and gene clusters in members of the genus and find the genes are limited to the nonpathogenic strains, whereas the genes are more widely distributed among members of the genus. Our results provide new information on the antibiotic resistance mechanisms of species and highlight the importance of efflux pumps for saprophytic bacteria existing in multispecies communities. Antibiotic efflux pumps are best known for increasing antibiotic resistance of pathogens; however, the role of these pumps in saprophytes is much less well defined. This study describes two predicted efflux pump gene clusters in the genus, which is comprised of both nonpathogenic saprophytes and species that cause highly fatal human infections. One of the predicted efflux pump clusters is present in every member of the genus and increases resistance to a broad range of antibiotics. The other gene cluster has more narrow antibiotic specificity and is found only in , a subset of entirely nonpathogenic species. We demonstrate the role of both pumps in increasing antibiotic resistance and demonstrate the importance of efflux-dependent resistance induction for survival in a dual-species competition model. These results have implications for managing antibiotic-resistant infections and for understanding the evolution of efflux pumps outside the host.