An RpoH-Like Heat Shock Sigma Factor Is Involved in Stress Response and Virulence in Brucella melitensis 16M

B. melitensis 16M genome analysis revealed the presence of six putative sigma factor-encoding genes: rpoD , rpoH1 , rpoH2 , rpoE1 , rpoE2 , and rpoN . We mutated all these genes except rpoD . Phenotypic analysis of the mutants reveals that a strain carrying an rpoH2 null mutation (Δ rpoH2 ) is impaired for growth at 21 and 42°C and shows increased sensitivity to hydrogen peroxide. Compared to the wild-type strain, the Δ rpoH2 mutant is attenuated in all virulence models tested. Three other null mutants (Δ rpoH1 , Δ rpoE1 , and Δ rpoE2 mutants) are also defective for survival in mice at 4 weeks postinfection. We also demonstrated that rpoH2 deletion strongly reduces the expression of two major virulence factors in B. melitensis , the type IV secretion system and the flagellum.