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Infection and Immunity, June 2007, p. 2811-2817, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.00304-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

RNA Interference-Mediated Silencing of the YPS3 Gene of Histoplasma capsulatum Reveals Virulence Defects

Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53706

Received 23 February 2007/ Returned for modification 6 March 2007/ Accepted 28 March 2007

The YPS3 gene of Histoplasma capsulatum encodes a protein that is both surface localized in the cell wall of H. capsulatum and released into the culture medium. This protein is produced only during the pathogenic yeast phase of infection and is also expressed differentially in H. capsulatum strains of different virulence levels. In this study, we silenced the YPS3 transcript by using an interfering-RNA strategy and examined the silenced mutants for phenotypic differences in vitro and during infection. The mutants showed no growth defect during in vitro culture in a defined medium at 37°C and appeared to have normal virulence in a RAW 264.7 murine macrophage-like cell line. In a C57BL/6 mouse model of infection, however, the mutants caused significantly decreased fungal burdens, particularly in the peripheral phagocyte-rich tissues of livers and spleens. This defect in organ colonization was evident within 3 days of infection; however, it appeared to be exacerbated at later time points.

Published ahead of print on 2 April 2007.

Editor: A. Casadevall

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