Systematic review and new insights into the molecular characterization of the Candida rugosa species complex

Recently, Candida rugosa was characterized as a species complex comprising four taxa: C. rugosa sensu stricto, Candida pseudorugosa, Candida neorugosa and Candida mesorugosa. Although considered relatively rare, several clusters of candidemia due to C. rugosa complex had been reported presenting mortality rates close to 70%. In this work we discuss the systematization, phenotyping and molecular methods based on internal transcribed spacer region (ITS) sequencing and proteomic analyses for species identification, as well as clinical aspects of the C. rugosa complex. We performed a Bayesian phylogenetic analysis using 72 ITS sequences representative of C. rugosa complex isolates and related species within the genus. Biochemical, morphological and MALDI-TOF MS analyses were processed with C. rugosa complex type strains and related species isolates. We described that the phylogeny showed four distinct clades inferred with high posterior probabilities, corresponding to the four species within the C. rugosa complex, excluding C. pararugosa. Biochemical and morphological aspects distinguished only C. rugosa sensu stricto but were not sufficient to accurately identify species within the rest of the complex. Protein spectrum profiles differentiated all reference strains from different species analyzed. To our knowledge, we presented the first phylogenetic analysis using a large collection of ITS sequences as well as proteomic profiles generated from isolates of the C. rugosa complex and related species that can enlighten systematics, diagnostics and clinical research fields.