Functional specificity of Candida albicans Als3p proteins and clade specificity of ALS3 alleles discriminated by the number of copies of the tandem repeat sequence in the central domain

Abstract

Candida albicansstrain SC5314 contains twoALS3alleles, which differ in sequence with respect to the number of copies of the 108 bp tandem repeat sequence within the central domain of the coding region. One allele (ALS3(12)) has 12 tandem repeat copies while the other (ALS3(9)) has 9 copies. Wild-typeC. albicans(ALS3(12)/ALS3(9)) and those containing variousALS3alleles (ALS3(12)/als3Δ(9),als3Δ(12)/ALS3(9) andals3Δ(12)/als3Δ(9)) were assayed for adhesion to monolayers of cultured vascular endothelial and pharyngeal epithelial cells. These assays showed obvious adhesive function for the larger Als3p protein, compared to a minor contribution to adhesion from the smaller protein. These functional differences in strain SC5314 prompted examination ofALS3allelic diversity across the five major genetic clades ofC. albicans. This analysis focused on the number of copies of the tandem repeat sequence within the central domain of the coding region and showed a range of alleles encoding from 6 to 19 tandem repeat copies. Clades differed with respect to prevalentALS3alleles and allele distribution, but were similar for the mean number of tandem repeat copies perALS3allele. Analysis of allelic pairing showed clade differences and the tendency forC. albicansstrains to encode one longer and one shorterALS3allele. The allelic variability observed forALS3and its functional consequences observed in strain SC5314 highlight the importance of understanding ALS allelic diversity in order to draw accurate conclusions about Als protein function.