Adhesion in Candida spp.

Microbial adherence is one of the most important determinants of pathogenesis, yet very few adhesins have been identified from fungal pathogens. Four structurally related adhesins, Hwp1, Ala1p/Als5p, Als1p, from Candida albicans and Epa1p from Candida glabrata, are members of a class of proteins termed glycosylphosphatidylinositol-dependent cell wall proteins (GPI-CWP). These proteins have N-terminal signal peptides and C-terminal features that mediate glycosylphosphatidylinositol (GPI) membrane anchor addition, as well as other determinants leading to attachment to cell wall glucan. While common signalP/GPI motifs facilitate cell surface expression, unique features mediate ligand binding specificities of adhesins. The first glimpse of structural features of putative adhesins has come from biophysical characterizations of the N-terminal domain of Als5p. One protein not in the GPI-CWP class that was initially described as an adhesin, Int1p, has recently been shown to be similar to Bud4p of Saccharomyces cerevisiae in primary amino acid sequence, in co-localizing with septins and in functioning in bud site selection. Progress in understanding the role of adhesins in oroesophageal candidiasis has been made for Hwp1 in a study using beige athymic and transgenic epsilon 26 mice that have combined defects in innate and acquired immune responses. Searches of the C. albicans genome for proteins in the GPI-CWP class has led to the identification of a subset of genes that will be the focus of future efforts to identify new Candida adhesins.