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Infection and Immunity, August 2009, p. 3466-3474, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00444-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Eric S. Anderson,1,{ddagger} James T. Paulley,1,{dagger},{ddagger} Jennifer M. Gaines,1 Michelle W. Valderas,2,§ Daniel W. Martin,1 Evan Menscher,1 Timothy D. Brown,1 Colin S. Burns,3 and R. Martin Roop II1*

Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27834,1 Department of Veterinary Pathobiology, Oklahoma State University Center for Veterinary Health Sciences, Stillwater, Oklahoma 74078,2 Department of Chemistry, East Carolina University, Greenville, North Carolina 278583

Received 20 April 2009/ Returned for modification 3 May 2009/ Accepted 20 May 2009

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, East Carolina University School of Medicine, 600 Moye Boulevard, Greenville, NC 27834. Phone: (252) 744-1357. Fax: (252) 744-3535. E-mail: roopr{at}ecu.edu

{triangledown} Published ahead of print on 1 June 2009.

Editor: A. J. Bäumler

{ddagger} Eric S. Anderson and James T. Paulley contributed equally to this work.

{dagger} Present address: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40506.

§ Present address: Lovelace Respiratory Research Institute, Albuquerque, NM 87108.

Infection and Immunity, August 2009, p. 3466-3474, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00444-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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