The URA5 Gene Is Necessary for Histoplasma capsulatum Growth during Infection of Mouse and Human Cells
| Autor: | Diane M. Retallack, Elizabeth L. Heinecke, Jon P. Woods, Reta S. Gibbons, George S. Deepe |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Pyrimidine Orotate Phosphoribosyltransferase Auxotrophy Genes Fungal Histoplasma Immunology Virulence medicine.disease_cause Microbiology Cell Line Mice chemistry.chemical_compound medicine Animals Humans Uracil Histoplasmosis Gene Mutation biology U937 Cells bacterial infections and mycoses biology.organism_classification Mice Inbred C57BL Infectious Diseases chemistry Cell culture Parasitology Fungal and Parasitic Infections |
| Zdroj: | Infection and Immunity. 67:624-629 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.67.2.624-629.1999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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