Candida albicans ALS1: domains related to a Saccharomyces cerevisiae sexual agglutinin separated by a repeating motif

Abstract

Transfer of budding Candida albicans yeast cells from the rich, complex medium YEPD to the defined tissue culture medium RPMI 1640 (RPMI) at 37 degrees C and 5% CO2 causes rapid onset of hyphal induction. Among the genes induced under these conditions are hyphal-specific genes as well as genes expressed in response to changes in temperature, CO2 and specific media components. A cDNA library constructed from cells incubated for 20 min in RPMI was differentially screened with yeast (YEPD)- and hyphal (RPMI)-specific probes resulting in identification of a gene expressed in response to culture conditions but not regulated by the yeast-hyphal transition. The deduced gene product displays significant identity to Saccharomyces cerevisiae alpha-agglutinin, encoded by AG alpha 1, an adhesion glycoprotein that mediates mating of haploid cells. The presence of this gene in C. albicans is curious since the organism has not been observed to undergo meiosis. We designate the C. albicans gene ALS1 (for agglutinin-like sequence). While the N- and C-termini of the predicted 1260-amino-acid ALS1 protein resemble those of the 650-amino-acid AG alpha 1, ALS1 contains a central domain of tandem repeats consisting of a highly conserved 36-amino-acid sequence not present in AG alpha 1. These repeats are also present on the nucleotide level as a highly conserved 108 bp motif. Southern and Northern blot analyses indicate a family of C. albicans genes that contain the tandem repeat motif; at least one gene in addition to ALS1 is expressed under conditions similar to those for ALS1 expression. Genomic Southern blots from several C. albicans isolates indicate that the number of copies of the tandem repeat element in ALS1 differs across strains and, in some cases, between ALS1 alleles in the same strain, suggesting a strain-dependent variability in ALS1 protein size. Potential roles for the ALS1 protein are discussed.

Multiple Functions of Pmt1p-mediated ProteinO-Mannosylation in the Fungal Pathogen Candida albicans

“…The calcofluor white phenotype suggests that O-glycosylation of unknown proteins by Pmt1p stabilizes the C. albicans cell wall. In our study, we identified the Als1 protein (44), which recently has been recognized as a potential adhesion factor for C. albicans (45), as the first likely O-glycosylated protein in the cell wall of C. albicans. Recent results suggest that PMT1 activity is required to incorporate several proteins into the cell wall of S. cerevisiae (54).…”

The Candida albicans pH-regulated KER1 gene encodes a lysine/glutamic-acid-rich plasma-membrane protein that is involved in cell aggregation

“…Molecular genetic approaches have identified several genes encoding hypha-specific cell-surface proteins that may contribute to differences in cell-wall structure or function in C. albicans (Hoyer et al, 1995;Staab et al, 1996). In this context, immunoscreening of a cDNA library with a germtube-specific polyclonal antibody (Casanova et al, 1989) led to the isolation of a novel gene, designated KER1, encoding a putative polypeptide of 1197 amino acids, rich in lysine (14?5 %) and glutamic acid (16?7 %).…”

ALS3 and ALS8 represent a single locus that encodes a Candida albicans adhesin; functional comparisons between Als3p and Als1p

“…A GFP probe fragment amplified from pGFP-URA3 with primers GFPXhoI and GFPBglII was also used to verify constructs. Fluorescence of correct clones was monitored microscopically following growth in media conditions shown previously by Northern blotting to increase transcription from the ALS1 and ALS3 promoters (Hoyer et al, 1995(Hoyer et al, , 1998. Expression patterns matching previous Northern blot results confirmed that the clones displayed GFP production under control of the correct promoter.…”

“…The emergence of initial functional data for Als1p and Als5p is important because they have the most similar N-terminal domain sequences (87 % amino acid identity) within the ALS family (Hoyer et al, 1995;Gaur & Klotz, 1997;Hoyer & Hecht, 2000;Fu et al, 2002). The sequence of Als3p is also closely related to Als1p (84 % amino acid identity) and Als5p (81 % amino acid identity) within the N-terminal domain (Hoyer et al, 1998).…”