Evolution and genome divergence determine virulence traits in Candida spp.

Candida albicans and Candida parapsilosis are known as the most causative agents of human fungal infections, but in healthy conditions they colonize the human gastrointestinal tract as commensals. While the pathogenicity of C. albicans is associated to the phenotype switch -with conversion from white to opaque colony and from cell to hyphae- affecting a variety of virulence-related genetic factors, for C. parapsilosis the genetic makeup associated to the virulence is still unknown. In order to investigate the intra and inter-species variability involved in the phenotypical changes we analyze the whole genome sequences of 7 candida strains (3 of C. albicans and 4 of C. parapsilosis) isolated from fecal samples of healthy and Crohn's disease patients, a severe inflammatory bowel disease. The results show two different population Evolutionary Genomics and Bioinformatics 19 structures: while C. albicans present an extreme variability and divergence between strains, C. parapsilosi sseems to be more clonal, with very low number of polymorphisms. Notably, in C. albicanan intriguing genomic plasticity have been observed. Indeed, over the high polymorphism, strain-specific gene losses, acquisition, and several miss-sense genes were found. Moreover, in C. albicans isolates, the most polymorphic genes codify proteins related to the cell wall and hyphal formation, external encapsulation structure and cell periphery, suggesting a continuous adaptation to adverse environments or stress conditions. Our data are confirmed by phenotypical characterization that show changes in virulence related traits (invasive growth, hyphal formation and switch from smooth to myceliated colonies) for the majority of C. albicans strains. Also in two C. parapsilosis strains similar pathogenic traits were found. Interestingly, the cytokine milieu released by human PBMCs and DCs showed that specific inflammatory responses are produced by strains with the most virulent phenotype. Overall these results provide significant insights regarding the link between host adaptation, pathogenesis and evolution