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Infection and Immunity, April 2006, p. 2373-2381, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2373-2381.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Deletion of the CaBIG1 Gene Reduces ß-1,6-Glucan Synthesis, Filamentation, Adhesion, and Virulence in Candida albicans

Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo 162-8640,¹ Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, Osaka 558-8585,² Department of Pathobiology, Nihon University School of Veterinary Medicine, Kanagawa 252-8510, Japan³

Received 17 October 2005/ Returned for modification 27 November 2005/ Accepted 24 January 2006

The human fungal pathogen Candida albicans is able to change its shape in response to various environmental signals. We analyzed the C. albicans BIG1 homolog, which might be involved in ß-1,6-glucan biosynthesis in Saccharomyces cerevisiae. C. albicans BIG1 is a functional homolog of an S. cerevisiae BIG1 gene, because the slow growth of an S. cerevisiae big1 mutant was restored by introduction of C. albicans BIG1. CaBig1p was expressed constitutively in both the yeast and hyphal forms. A specific localization of CaBig1p at the endoplasmic reticulum or plasma membrane similar to the subcellular localization of S. cerevisiae Big1p was observed in yeast form. The content of ß-1,6-glucan in the cell wall was decreased in the Cabig1 strain in comparison with the wild-type or reconstituted strain. The C. albicans BIG1 disruptant showed reduced filamentation on a solid agar medium and in a liquid medium. The Cabig1 mutant showed markedly attenuated virulence in a mouse model of systemic candidiasis. Adherence to human epithelial HeLa cells and fungal burden in kidneys of infected mice were reduced in the Cabig1 mutant. Deletion of CaBIG1 abolished hyphal growth and invasiveness in the kidneys of infected mice. Our results indicate that adhesion failure and morphological abnormality contribute to the attenuated virulence of the Cabig1 mutant.

Editor: A. Casadevall

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