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Eukaryotic Cell, November 2007, p. 2046-2055, Vol. 6, No. 11
1535-9778/07/$08.00+0     doi:10.1128/EC.00314-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Requirement for Candida albicans Sun41 in Biofilm Formation and Virulence{triangledown}

Carmelle T. Norice,1 Frank J. Smith Jr.,1 Norma Solis,2 Scott G. Filler,2,3 and Aaron P. Mitchell1*

Department of Microbiology, Columbia University, New York, New York,1 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California,2 The David Geffen School of Medicine at UCLA, Los Angeles, California3

Received 24 August 2007/ Accepted 2 September 2007

The cell wall of Candida albicans lies at the crossroads of pathogenicity and therapeutics. It contributes to pathogenicity through adherence and invasion; it is the target of both chemical and immunological antifungal strategies. We have initiated a dissection of cell wall function through targeted insertional mutagenesis of cell wall-related genes. Among 25 such genes, we were unable to generate homozygous mutations in 4, and they may be essential for viability. We created homozygous mutations in the remaining 21 genes. Insertion mutations in SUN41, Orf19.5412, Orf19.1277, MSB2, Orf19.3869, and WSC1 caused hypersensitivity to the cell wall inhibitor caspofungin, while two different ecm33 insertions caused mild caspofungin resistance. Insertion mutations in SUN41 and Orf19.5412 caused biofilm defects. Through analysis of homozygous sun41{Delta}/sun41{Delta} deletion mutants and sun41{Delta}/sun41{Delta}+pSUN41-complemented strains, we verified that Sun41 is required for biofilm formation and normal caspofungin tolerance. The sun41{Delta}/sun41{Delta} mutant had altered expression of four cell wall damage response genes, thus suggesting that it suffers a cell wall structural defect. Sun41 is required for inducing disease, because the mutant was severely attenuated in mouse models of disseminated and oropharyngeal candidiasis. Although the mutant produced aberrant hyphae, it had no defect in damaging endothelial or epithelial cells, unlike many other hypha-defective mutants. We suggest that the sun41{Delta}/sun41{Delta} cell wall defect is the primary cause of its attenuated virulence. As a small fungal surface protein with predicted glucosidase activity, Sun41 represents a promising therapeutic target.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University, New York, NY. Phone: (212) 305-8251. Fax: (212) 305-1468. E-mail: apm4{at}columbia.edu

{triangledown} Published ahead of print on 14 September 2007.

Eukaryotic Cell, November 2007, p. 2046-2055, Vol. 6, No. 11
1535-9778/07/$08.00+0     doi:10.1128/EC.00314-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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