Previous findings indicate thatBrucellosis, an infectious disease affecting livestock and humans, is caused by different species of the genus Brucella, which belongs to the alpha-2 subgroup of the Proteobacteria. This subgroup also includes genera normally nonpathogenic for humans, such as Agrobacterium, Rhizobium, and Ochrobactrum (24). In contrast to Brucella species, which infect animals and humans, other alphaproteobacteria usually live in the soil (Ochrobactrum), establish symbiotic relationships with plants (Rhizobium, Mesorhizobium, and Sinorhizobium species) (19), or are phytopathogens (Agrobacterium) (29). These related alphaproteobacteria are not pathogenic for immunocompetent individuals or show only a limited pathogenicity. Human infections with Agrobacterium tumefaciens (Agrobacterium radiobacter) and Ochrobactrum anthropi have been reported almost exclusively to occur in immunocompromised patients or in those with debilitating underlying diseases or undergoing chemotherapy (2, 3, 21). There are no reports of human disease by Rhizobium and other nodule-forming bacteria.The close genetic and antigenic relationship between Brucella and nonpathogenic alphaproteobacteria (NPAP) has been revealed by several studies. A total of 1,902 Brucella suis open reading frames are conserved in Mesorhizobium loti, Sinorhizobium meliloti, and Agrobacterium tumefaciens, and 2,408 B. suis open reading frames are conserved in at least one of these three genomes (25). Similar relationships have been observed between NPAP and Brucella melitensis and Brucella abortus, since the genomes of the last two species are highly similar to that of B. suis (13,17).Few studies have investigated the immunological cross-reactivity between proteins from Brucella and those from related alphaproteobacteria. Velasco et al. (30) found an extensive cross-reactivity between cytosolic proteins from Brucella melitensis and those from Ochrobactrum anthropi and also some cross-reactions at the level of outer membrane proteins and lipopolysaccharide. More recently, we have shown the existence of cross-reactivities between Brucella and other NPAP, including Sinorhizobium meliloti and Agrobacterium tumefaciens (12). Moreover, we showed that some of these cross-reactivities could potentially be exploited for the development of serological tests for brucellosis based on antigens from NPAP.Live attenuated Brucella strains are still widely used for the vaccination of animals against brucellosis. While these vaccines have reduced virulence for animals, they still can produce disease in humans (4,5,6,27). Therefore, large-scale production of such vaccines requires biosafety level 3 facilities (11), which are seldom available in developing countries, where brucellosis is more prevalent. This is one of the reasons that has led many researchers to investigate alternative vaccination strategies for brucellosis, including the use of subunit vaccines based on recombinant proteins (1, 15) or the use of DNA
