Brucella abortus, a mammalian pathogen, and Rhizobium meliloti, a phylogenetically related plant symbiont, establish chronic infections in their respective hosts. Here a highly conserved B, abortus homolog of the R, meliloti bacA gene, which encodes a putative cytoplasmic membrane transport protein required for symbiosis, was identified. An isogenic B, abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain. Thus, the bacA gene product is critical for the maintenance of two very diverse host-bacterial relationships.