This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Retallack, D. M.
Right arrow Articles by Woods, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Retallack, D. M.
Right arrow Articles by Woods, J. P.

 Previous Article  |  Next Article 

Infection and Immunity, February 1999, p. 624-629, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The URA5 Gene Is Necessary for Histoplasma capsulatum Growth during Infection of Mouse and Human Cells

Diane M. Retallack,1 Elizabeth L. Heinecke,1 Reta Gibbons,2 George S. Deepe Jr.,2 and Jon P. Woods1,*

Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53706,1 and Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio 452672

Received 25 August 1998/Returned for modification 29 October 1998/Accepted 9 November 1998

The Histoplasma capsulatum URA5 gene, which has recently been cloned and disrupted by allelic replacement, encodes orotidine-5'-monophosphate pyrophosphorylase. Inactivation of URA5 by either targeted or UV mutagenesis results in disruption of the pyrimidine biosynthetic pathway and uracil auxotrophy. We examined the effect of uracil auxotrophy due to a ura5 mutation on H. capsulatum virulence in both cell culture and whole-animal models. Uracil auxotrophs of two H. capsulatum restriction fragment length polymorphism classes were found to be avirulent in cultured murine and human cells, as well as in mice. Moreover, virulence could be restored either by supplying a functional URA5 gene in trans or by supplying exogenous uracil during infection in vitro. These experiments demonstrate that the pyrimidine biosynthetic pathway is essential for H. capsulatum growth and virulence.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, 420 SMI, University of Wisconsin Medical School, 1300 University Ave., Madison, WI 53706-1532. Phone: (608) 265-6292. Fax: (608) 265-6132. E-mail: jpwoods{at}facstaff.wisc.edu.

Infection and Immunity, February 1999, p. 624-629, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Cooper, K. G., Woods, J. P. (2009). Secreted Dipeptidyl Peptidase IV Activity in the Dimorphic Fungal Pathogen Histoplasma capsulatum. Infect. Immun. 77: 2447-2454 [Abstract] [Full Text]  
  • Costa, M., Borges, C. L., Bailao, A. M., Meirelles, G. V., Mendonca, Y. A., Dantas, S. F. I. M., de Faria, F. P., Felipe, M. S. S., Molinari-Madlum, E. E. W. I., Mendes-Giannini, M. J. S., Fiuza, R. B., Martins, W. S., Pereira, M., Soares, C. M. A. (2007). Transcriptome profiling of Paracoccidioides brasiliensis yeast-phase cells recovered from infected mice brings new insights into fungal response upon host interaction. Microbiology 153: 4194-4207 [Abstract] [Full Text]  
  • Bohse, M. L., Woods, J. P. (2007). RNA Interference-Mediated Silencing of the YPS3 Gene of Histoplasma capsulatum Reveals Virulence Defects. Infect. Immun. 75: 2811-2817 [Abstract] [Full Text]  
  • Bohse, M. L., Woods, J. P. (2007). Expression and Interstrain Variability of the YPS3 Gene of Histoplasma capsulatum. Eukaryot Cell 6: 609-615 [Abstract] [Full Text]  
  • Rooney, P. J., Klein, B. S. (2004). Sequence Elements Necessary for Transcriptional Activation of BAD1 in the Yeast Phase of Blastomyces dermatitidis. Eukaryot Cell 3: 785-794 [Abstract] [Full Text]  
  • Sebghati, T. S., Engle, J. T., Goldman, W. E. (2000). Intracellular Parasitism by Histoplasma capsulatum: Fungal Virulence and Calcium Dependence. Science 290: 1368-1372 [Abstract] [Full Text]  
  • Fisher, K. L., Deepe, G. S. Jr., Woods, J. P. (1999). Histoplasma capsulatum Strain Variation in Both H Antigen Production and beta -Glucosidase Activity and Overexpression of HAG1 from a Telomeric Linear Plasmid. Infect. Immun. 67: 3312-3316 [Abstract] [Full Text]  


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