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Infection and Immunity, May 2006, p. 2925-2936, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2925-2936.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Attenuated Bioluminescent Brucella melitensis Mutants GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091) Confer Protection in Mice

Gireesh Rajashekara,1 David A. Glover,1 Menachem Banai,2 David O'Callaghan,3 and Gary A. Splitter1*

Department of Animal Health and Biomedical Sciences, University of Wisconsin—Madison, 1656 Linden Drive, Madison, Wisconsin 53706,1 Department of Bacteriology, Kimron Veterinary Institute, P.O. Box 12, Bet Dagan 50250, Israel,2 INSERM U431, UFR Médecine, CS83021, Avenue Kennedy, 30908 Nimes Cedex 02, France3

Received 19 January 2006/ Returned for modification 12 February 2006/ Accepted 20 February 2006

In vivo bioluminescence imaging is a persuasive approach to investigate a number of issues in microbial pathogenesis. Previously, we have applied bioluminescence imaging to gain greater insight into Brucella melitensis pathogenesis. Endowing Brucella with bioluminescence allowed direct visualization of bacterial dissemination, pattern of tissue localization, and the contribution of Brucella genes to virulence. In this report, we describe the pathogenicity of three attenuated bioluminescent B. melitensis mutants, GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091), and the dynamics of bioluminescent virulent bacterial infection following vaccination with these mutants. The virB4, galE, and BMEI1090-BMEI1091 mutants were attenuated in interferon regulatory factor 1-deficient (IRF-1–/–) mice; however, only the GR019 (virB4) mutant was attenuated in cultured macrophages. Therefore, in vivo imaging provides a comprehensive approach to identify virulence genes that are relevant to in vivo pathogenesis. Our results provide greater insights into the role of galE in virulence and also suggest that BMEI1090 and downstream genes constitute a novel set of genes involved in Brucella virulence. Survival of the vaccine strain in the host for a critical period is important for effective Brucella vaccines. The galE mutant induced no changes in liver and spleen but localized chronically in the tail and protected IRF-1–/– and wild-type mice from virulent challenge, implying that this mutant may serve as a potential vaccine candidate in future studies and that the direct visualization of Brucella may provide insight into selection of improved vaccine candidates.

* Corresponding author. Mailing address: Department of Animal Health and Biomedical Sciences, University of Wisconsin—Madison, 1656 Linden Drive, Madison, WI 53706. Phone: (608) 262-1837. Fax: (608) 262-7420. E-mail: splitter{at}svm.vetmed.wisc.edu.

Editor: D. L. Burns

Infection and Immunity, May 2006, p. 2925-2936, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2925-2936.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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