This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Lindgren, H.
Right arrow Articles by Sjöstedt, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lindgren, H.
Right arrow Articles by Sjöstedt, A.

 Previous Article  |  Next Article 

Infection and Immunity, October 2009, p. 4429-4436, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00702-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The 58-Kilodalton Major Virulence Factor of Francisella tularensis Is Required for Efficient Utilization of Iron{triangledown}

Helena Lindgren,1 Marie Honn,1 Igor Golovlev,1 Konstantin Kadzhaev,1 Wayne Conlan,2 and Anders Sjöstedt1*

Department of Clinical Microbiology, Clinical Bacteriology, and Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden,1 National Research Council Canada, Institute for Biological Sciences, Ottawa, Canada2

Received 22 June 2009/ Returned for modification 13 July 2009/ Accepted 20 July 2009

We investigated the role of the 58-kDa FTT0918 protein in the iron metabolism of Francisella tularensis. The phenotypes of SCHU S4, a prototypic strain of F. tularensis subsp. tularensis, and the {Delta}FTT0918 and {Delta}fslA isogenic mutants were analyzed. The gene product missing in the {Delta}fslA mutant is responsible for synthesis of a siderophore. When grown in broth with various iron concentrations, the two deletion mutants generally reached lower maximal densities than SCHU S4. The {Delta}FTT0918 mutant, but not the {Delta}fslA mutant, upregulated the genes of the F. tularensis siderophore locus (fsl) operon even at high iron concentrations. A chrome azurol sulfonate plate assay confirmed siderophore production by all strains except the {Delta}fslA strain. In a cross-feeding experiment using medium devoid of free iron, SCHU S4 promoted growth of the {Delta}fslA strain but not of the {Delta}FTT0918 strain. The sensitivity of SCHU S4 and the {Delta}FTT0918 and {Delta}fslA strains to streptonigrin demonstrated that the {Delta}FTT0918 strain contained a smaller free intracellular iron pool and that the {Delta}fslA strain contained a larger one than SCHU S4. In contrast to the marked attenuation of the {Delta}FTT0918 strain, the {Delta}fslA strain was as virulent as SCHU S4 in a mouse model. Altogether, the data demonstrate that the FTT0918 protein is required for F. tularensis to utilize iron bound to siderophores and that it likely has a role also in siderophore-independent iron acquisition. We suggest that the FTT0918 protein be designated Fe utilization protein A, FupA.

* Corresponding author. Mailing address: Department of Clinical Bacteriology and Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-901 85 Umeå, Sweden. Phone: 46-90-785 1120. Fax: 46-90-785 2225. E-mail: anders.sjostedt{at}climi.umu.se

{triangledown} Published ahead of print on 3 August 2009.

Editor: A. J. Bäumler

Infection and Immunity, October 2009, p. 4429-4436, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00702-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»