Abstract

We investigated genomic diversity of a yeast species that is both an opportunistic pathogen and an important industrial yeast. Under the name Candida krusei, it is responsible for about 2% of yeast infections caused by Candida species in humans. Bloodstream infections with C. krusei are problematic because most isolates are fluconazole-resistant. Under the names Pichia kudriavzevii, Issatchenkia orientalis and Candida glycerinogenes, the same yeast, including genetically modified strains, is used for industrial-scale production of glycerol and succinate. It is also used to make some fermented foods. Here, we sequenced the type strains of C. krusei (CBS573T) and P. kudriavzevii (CBS5147T), as well as 30 other clinical and environmental isolates. Our results show conclusively that they are the same species, with collinear genomes 99.6% identical in DNA sequence. Phylogenetic analysis of SNPs does not segregate clinical and environmental isolates into separate clades, suggesting that C. krusei infections are frequently acquired from the environment. Reduced resistance of strains to fluconazole correlates with the presence of one gene instead of two at the ABC11-ABC1 tandem locus. Most isolates are diploid, but one-quarter are triploid. Loss of heterozygosity is common, including at the mating-type locus. Our PacBio/Illumina assembly of the 10.8 Mb CBS573T genome is resolved into 5 complete chromosomes, and was annotated using RNAseq support. Each of the 5 centromeres is a 35 kb gene desert containing a large inverted repeat. This species is a member of the genus Pichia and family Pichiaceae (the methylotrophic yeasts clade), and so is only distantly related to other pathogenic Candida species.

Highlights

  • Pathogenic Candida species are ascomycete yeasts that cause over 46,000 invasive infections annually in the US alone, with a 30% mortality rate [1]

  • We examined the genomes of 20 clinical isolates (‘C. krusei’) and 12 environmental isolates (‘P. kudriavzevii’) and find that there is no genetic distinction between them

  • Our results show unequivocally that C. krusei and P. kudriavzevii are the same species, that clinical and environmental strains are not distinct, and that high levels of drug resistance are common in environmental isolates

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Summary

Introduction

Pathogenic Candida species are ascomycete yeasts that cause over 46,000 invasive infections annually in the US alone, with a 30% mortality rate [1]. The top five pathogenic Candida species in order of prevalence in invasive candidiasis worldwide are C. albicans (52% of infections), C. glabrata (21%), C. tropicalis (14%), C. parapsilosis (9%) and C. krusei (2%) (calculated from data in [2]). Uncommon in the normal human flora, C. krusei is sometimes carried intestinally by healthy individuals and in one remote Amerindian community it was found to be present in over 30% of the population, much higher than C. albicans, and was probably acquired from food or the environment [3]. As well as being associated with humans, C. krusei has been detected in feral pigeons and other wild animals [3, 4]

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