Null cyclic -1,2-glucan synthetase mutants (cgs mutants) were obtained from Brucella abortus virulent strain 2308 and from B. abortus attenuated vaccinal strain S19. Both mutants show greater sensitivity to surfactants like deoxycholic acid, sodium dodecyl sulfate, and Zwittergent than the parental strains, suggesting cell surface alterations. Although not to the same extent, both mutants display reduced virulence in mice and defective intracellular multiplication in HeLa cells. The B. abortus S19 cgs mutant was completely cleared from the spleens of mice after 4 weeks, while the 2308 mutant showed a 1.5-log reduction of the number of brucellae isolated from the spleens after 12 weeks. These results suggest that cyclic -1,2-glucan plays an important role in the residual virulence of the attenuated B. abortus S19 strain. Although the cgs mutant was cleared from the spleens earlier than the wild-type parental strain (B. abortus S19) and produced less inflammatory response, its ability to confer protection against the virulent strain B. abortus 2308 was fully retained. Equivalent levels of induction of spleen gamma interferon mRNA and anti-lipopolysaccharide (LPS) of immunoglobulin G2a (IgG2a) subtype antibodies were observed in mice injected with B. abortus S19 or the cgs mutant. However, the titer of anti-LPS antibodies of the IgG1 subtype induced by the cgs mutant was lower than that observed with the parental S19 strain, thus suggesting that the cgs mutant induces a relatively exclusive Th1 response.Brucella abortus is an intracellular pathogen that causes abortion in bovines and can infect humans. Abortion in cattle is the consequence of the tropism that the bacterium has for the placenta of pregnant animals, in which it multiplies intracellularly (10). Brucellosis in humans is primarily a disease of the reticuloendothelial system, in which the bacteria multiply inside the phagocytic cell; the intermittent release of bacteria from the cells into the bloodstream causes undulant fever (17, 29). Brucellosis does not spread among humans; consequently, eradication of the disease from the natural reservoirs, cattle, pigs, sheep, goats, and other susceptible animals, will lead to elimination of human infection. In regions with high prevalence of the disease, the only way of controlling and eventually eradicating this zoonosis is by vaccination of all susceptible hosts and elimination of infected animals.Vaccination represents an important tool for the control of bovine brucellosis. One of the most used vaccines is the attenuated strain B. abortus S19 obtained spontaneously from the virulent strain B. abortus 2308 (24, 25, 26, 29). Live attenuated B. abortus S19 has served for many years as an effective vaccine to prevent brucellosis in cattle (8,18). The genetic defect that leads to attenuation of this strain has not yet been defined. B. abortus S19 has lost some essential unknown mechanism of virulence. Despite this fact, the vaccinal strain conserves some degree of virulence, being pathogenic for humans (37), and...