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Eukaryotic Cell, March 2009, p. 373-387, Vol. 8, No. 3
1535-9778/09/$08.00+0     doi:10.1128/EC.00387-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Property Differences among the Four Major Candida albicans Strain Clades {triangledown} ,{dagger}

Donna M. MacCallum, Luis Castillo, Kerstin Nather, Carol A. Munro, Alistair J. P. Brown, Neil A. R. Gow, and Frank C. Odds*

Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom

Received 12 December 2008/ Accepted 8 January 2009

A selection of 43 Candida albicans isolates, chosen to represent the four major strain clades of the species and also intraclade diversity, was screened for their virulence in the murine intravenous challenge model of C. albicans infection, for a range of properties measurable in vitro that might relate to virulence, and for the numbers of midrepeat sequences in genes of the ALS and HYR families. Heterozygosity at the mating type locus and low whole-cell acid phosphatase activity and growth rate at 40°C were found to be significantly positively associated with the most virulent isolates. Acid phosphatase activity and growth in 2 M NaCl were statistically significant variables between clades by univariate analysis. Isolates in different clades also differed significantly in midrepeat sequence alleles of ALS2, ALS4, ALS6, ALS7, ALS9, HYR1, and HYR2. There was no association between the midrepeat alleles of any ALS or HYR gene and the virulence of isolates to mice. Genome-wide transcript profiles of 20 isolates (5 per clade) grown under two conditions showed considerable variation between individual isolates, but only a small number of genes showed statistically significant differential gene expression between clades. Analysis of the expression profiles by overall strain virulence revealed 18 open reading frames differing significantly between isolates of high, intermediate, and low virulence. Four of these genes encoded functions related to phosphate uptake and metabolism. This finding and the significant association between whole-cell acid phosphatase activity and virulence led us to disrupt PHO100, which encodes a predicted periplasmic acid phosphatase. The pho100{Delta} mutant was mildly but significantly attenuated in terms of survival curves in the mouse model. The study has extended the range of properties known to differ between C. albicans clades and suggests a possible but minor role of phosphate metabolism in the virulence of the species.

* Corresponding author. Mailing address: Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom. Phone and fax: 44 1224 555828. E-mail: f.odds{at}abdn.ac.uk

{triangledown} Published ahead of print on 16 January 2009.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, March 2009, p. 373-387, Vol. 8, No. 3
1535-9778/09/$08.00+0     doi:10.1128/EC.00387-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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