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Infection and Immunity, April 2000, p. 1997-2002, Vol. 68, No. 4
Harbor-UCLA Research and Education Institute,
Torrance, California 905021; Department
of Microbiology and Immunology, School of Medicine, Georgetown
University Medical Center, Washington, D.C.
200072; and Departments of
Pathology3 and
Medicine,4 UCLA School of Medicine, Los
Angeles, California 90024
Received 1 December 1999/Accepted 21 December 1999
The Candida albicans gene HWP1 encodes a
surface protein that is required for normal hyphal development in
vitro. We used mutants lacking one or both alleles of HWP1
to investigate the role of this gene in virulence. Mice infected
intravenously with the homozygous hwp1 null mutant, CAL3,
survived a median of >14 days, whereas mice infected with a control
strain containing two functional alleles of HWP1 survived
only 3.5 days. After 1 day of infection, all strains produced similar
levels of infection in the kidneys, spleen, and blood. However, after 2 and 3 days, there was a significant decrease in the number of organisms
in the kidneys of the mice infected with CAL3. This finding suggests that the hwp1 homozygous null mutant is normal in its
ability to initiate infection but deficient in its capacity to maintain infection. CAL3 also germinated minimally in the kidneys. The ability
of the heterozygous null mutant to germinate and cause mortality in
mice was intermediate to CAL3, suggesting a gene dosage effect. To
investigate potential mechanisms for the diminished virulence of CAL3,
we examined its interactions with endothelial cells and neutrophils in
vitro. CAL3 caused less endothelial cell injury than the heterozygous
hwp1 mutant. We conclude that the HWP1 gene
product is important for both in vivo hyphal development and
pathogenicity of C. albicans. Also, the ability to form
filaments may be critical for candidal virulence by enabling the fungus to induce cellular injury and maintain a deep-seated infection.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Reduced Virulence of HWP1-Deficient
Mutants of Candida albicans and Their Interactions with
Host Cells

*
Corresponding author. Mailing address: Division of
Infectious Diseases, Harbor-UCLA Research and Education Institute, 1124 West Carson St., RB-2, Torrance, CA 90502. Phone: (310) 222-6426. Fax:
(310) 782-2016. E-mail: sfiller{at}ucla.edu.
Present address: Pharmacology Laboratories, Takeda Chemical
Industries, Ltd., Osaka, Japan.
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