Parallel Expansion and Divergence of the Hyr/Iff-like (Hil) Adhesin Family in Pathogenic Yeasts Including Candida auris

Abstract

Opportunistic yeast pathogens evolved multiple times in the Saccharomycetes class. A recent example is Candida auris, a multidrug resistant pathogen associated with a high mortality rate and multiple hospital outbreaks. Genomic changes shared between independently evolved pathogens could reveal key factors that enable them to infect the host. One such change may be the expansion of cell wall adhesins, which mediate biofilm formation and adherence and are established virulence factors in Candida spp. Here we show that homologs of a known adhesin family in C. albicans, the Hyr/Iff-like (Hil) family, repeatedly expanded in divergent pathogenic Candida lineages including in C. auris. Evolutionary analyses reveal varying levels of selective constraint and a potential role of positive selection acting on the ligand-binding domain during the family expansion in C. auris. The repeat-rich central domain evolved rapidly after gene duplication, leading to large variation in protein length and β-aggregation potential, both known to directly affect adhesive functions. Within C. auris, isolates from the less virulent Clade II lost five of the eight Hil homologs, while other clades show abundant tandem repeat copy number variation. We hypothesize that expansion and diversification of adhesin gene families are a key step towards the evolution of fungal pathogens and that variation in the adhesin repertoire could contribute to within and between species differences in the adhesive and virulence properties.