The virB operon is essential for lethality of Brucella microti in the Balb/c murine model of infection

In murine infections, Brucella microti exhibits an atypical and highly pathogenic behavior resulting in a mortality of 82%. In this study, the possible involvement of the virB type IV secretion system, a key virulence factor of Brucella sp., in this lethal phenotype was investigated. As previously described for B. suis, expression of the virB operon of B. microti was induced in acid minimal medium, partially mimicking intracellular environment. Early neutralization of cellular compartments abolished intracellular replication of B. microti, showing that acidity of the Brucella-containing vacuole is an essential trigger. A ΔvirB mutant of B. microti exhibited strong attenuation in murine and human macrophages in vitro. Interestingly, infection with this mutant was not lethal in Balb/c mice and lacked the typical intrasplenic peak at 3 days post-infection, hence demonstrating that lethality of B. microti in murine infection absolutely requires a functional virB operon.