Manganese Transporter MntH Is a Critical Virulence Determinant for Brucella abortus 2308 in Experimentally Infected Mice

• Published in: Infection and Immunity 2009-08, Vol.77 (8), p.3466-3474
• Main Authors: Anderson, Eric S, Paulley, James T, Gaines, Jennifer M, Valderas, Michelle W, Martin, Daniel W, Menscher, Evan, Brown, Timothy D, Burns, Colin S, Roop, R. Martin II
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Infections; Bacterial Proteins - physiology; Bacteriology; Biological and medical sciences; Brucella abortus; Brucella abortus - pathogenicity; Brucellosis - microbiology; Cation Transport Proteins - deficiency; Cation Transport Proteins - physiology; Cells, Cultured; Colony Count, Microbial; Cytoplasm - microbiology; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genetic Complementation Test; Genomes; Iron; Macrophages; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - microbiology; Manganese; Manganese - metabolism; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Nucleotide sequence; Replication; Repressors; Spleen - microbiology; Superoxide dismutase; Virulence; Virulence Factors - deficiency; Virulence Factors - physiology; Zinc
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00444-09

The gene designated BAB1_1460 in the Brucella abortus 2308 genome sequence is predicted to encode the manganese transporter MntH. Phenotypic analysis of an isogenic mntH mutant indicates that MntH is the sole high-affinity manganese transporter in this bacterium but that MntH does not play a detectable role in the transport of Fe²⁺, Zn²⁺, Co²⁺, or Ni²⁺. Consistent with the apparent selectivity of the corresponding gene product, the expression of the mntH gene in B. abortus 2308 is repressed by Mn²⁺, but not Fe²⁺, and this Mn-responsive expression is mediated by a Mur-like repressor. The B. abortus mntH mutant MWV15 exhibits increased susceptibility to oxidative killing in vitro compared to strain 2308, and a comparative analysis of the superoxide dismutase activities present in these two strains indicates that the parental strain requires MntH in order to make wild-type levels of its manganese superoxide dismutase SodA. The B. abortus mntH mutant also exhibits extreme attenuation in both cultured murine macrophages and experimentally infected C57BL/6 mice. These experimental findings indicate that Mn²⁺ transport mediated by MntH plays an important role in the physiology of B. abortus 2308, particularly during its intracellular survival and replication in the host.