1887

Abstract

The ALS (gglutinin-ike equence) family includes eight genes ( to , and ) that share a common general organization, consisting of a relatively conserved 5′ domain, a central domain of tandemly repeated sequence units, and a 3′ domain of relatively variable length and sequence. To test the hypothesis that the cell-surface glycoproteins encoded by the ALS genes mediate contact between the fungal cell and host surfaces, a set of mutant strains was systematically constructed, each lacking one of the ALS sequences. Phenotypes of the mutant strains were evaluated, primarily using adhesion assays. is unique within the ALS family due to extensive allelic sequence variation within the 5′ domain that may result in functional differences between proteins encoded by and . Deletion of significantly reduces adhesion to human vascular endothelial cell monolayers. The mutation was complemented by reintegration of a wild-type copy of , but not , suggesting allelic functional differences. Complementation of the mutation with a gene fusion between the 5′ domain of and the tandem repeats and 3′ domain of also restored wild-type adhesion levels. Analysis of the Δ/Δ mutant phenotype in other assays demonstrated no significant difference from a control strain for adhesion to buccal epithelial cells or laminin-coated plastic plates. The Δ/Δ mutant did not show significant differences from the control for adhesion to or destruction of cells in the reconstituted human epithelium (RHE) disease model, or for cell-wall defects, germ-tube formation or biofilm formation in a catheter model. Analysis of allelic frequency in a collection of geographically diverse clinical isolates showed a distinct preference for allelic sequences, within both the 5′ and the 3′ domain of the coding region. These data suggest greater selective pressure to maintain the allele in isolates and imply its greater relative importance in host–pathogen interactions.

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2007-07-01
2020-04-03
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