Characterization of Virulence-Related Phenotypes in Candida Species of the CUG Clade

Abstract

ABSTRACTCandidaspecies cause a variety of mucosal and invasive infections and are, collectively, the most important human fungal pathogens in the developed world. The majority of these infections result from a few related species within the “CUG clade,” so named because they use a nonstandard translation for that codon. Some members of the CUG clade, such asCandida albicans, present significant clinical problems, whereas others, such asCandida(Meyerozyma)guilliermondii, are uncommon in patients. The differences in incidence rates are imperfectly correlated with virulence in animal models of infection, but comparative analyses that might provide an explanation for why some species are effective pathogens and others are not have been rare or incomplete. To better understand the phenotypic basis for these differences, we characterized eight CUG clade species—C. albicans,C. dubliniensis,C. tropicalis,C. parapsilosis,Clavispora lusitaniae,M. guilliermondii,Debaryomyces hansenii, andLodderomyces elongisporus—for host-relevant phenotypes, including nutrient utilization, stress tolerance, morphogenesis, interactions with phagocytes, and biofilm formation. Two species deviated from expectations based on animal studies and human incidence.C. dubliniensiswas quite robust, grouping in nearly all assays with the most virulent species,C. albicansandC. tropicalis, whereasC. parapsilosiswas substantially less fit than might be expected from its clinical importance. These findings confirm the utility ofin vitromeasures of virulence and provide insight into the evolution of virulence in the CUG clade.