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Infection and Immunity, April 2009, p. 1636-1648, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01339-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Burkholderia mallei tssM Encodes a Putative Deubiquitinase That Is Secreted and Expressed inside Infected RAW 264.7 Murine Macrophages{triangledown} ,{dagger}

John Shanks,1 Mary N. Burtnick,2 Paul J. Brett,2 David M. Waag,3 Kevin B. Spurgers,3 Wilson J. Ribot,3 Mark A. Schell,4 Rekha G. Panchal,3 Frank C. Gherardini,2 Keith D. Wilkinson,1 and David DeShazer3*

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322,1 Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,2 Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702-5011,3 Department of Microbiology, University of Georgia, Athens, Georgia 306024

Received 1 November 2008/ Returned for modification 8 December 2008/ Accepted 12 January 2009

Burkholderia mallei, a category B biothreat agent, is a facultative intracellular pathogen that causes the zoonotic disease glanders. The B. mallei VirAG two-component regulatory system activates the transcription of ~60 genes, including a large virulence gene cluster encoding a type VI secretion system (T6SS). The B. mallei tssM gene encodes a putative ubiquitin-specific protease that is physically linked to, and transcriptionally coregulated with, the T6SS gene cluster. Mass spectrometry and immunoblot analysis demonstrated that TssM was secreted in a virAG-dependent manner in vitro. Surprisingly, the T6SS was found to be dispensable for the secretion of TssM. The C-terminal half of TssM, which contains Cys and His box motifs conserved in eukaryotic deubiquitinases, was purified and biochemically characterized. Recombinant TssM hydrolyzed multiple ubiquitinated substrates and the cysteine at position 102 was critical for enzymatic activity. The tssM gene was expressed within 1 h after uptake of B. mallei into RAW 264.7 murine macrophages, suggesting that the TssM deubiquitinase is produced in this intracellular niche. Although the physiological substrate(s) is currently unknown, the TssM deubiquitinase may provide B. mallei a selective advantage in the intracellular environment during infection.

* Corresponding author. Mailing address: Bacteriology Division, USAMRIID, 1425 Porter St., Fort Detrick, MD 21702. Phone: (301) 619-4871. Fax: (301) 619-8351. E-mail: david.deshazer{at}amedd.army.mil

{triangledown} Published ahead of print on 21 January 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Camilli

Infection and Immunity, April 2009, p. 1636-1648, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01339-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Burtnick, M. N., DeShazer, D., Nair, V., Gherardini, F. C., Brett, P. J. (2010). Burkholderia mallei Cluster 1 Type VI Secretion Mutants Exhibit Growth and Actin Polymerization Defects in RAW 264.7 Murine Macrophages. Infect. Immun. 78: 88-99 [Abstract] [Full Text]  
  • Wilkinson, K. D. (2009). DUBs at a glance. J. Cell Sci. 122: 2325-2329 [Full Text]  


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