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Genomes Confirm Food Industry Yeast Belongs to Same Species as Opportunistic Pathogen

NEW YORK (GenomeWeb) – New research suggests a yeast species used for fermentation and other food industry applications is nearly genetically identical to a drug-resistant yeast species that is classified as an opportunistic human pathogen.

Researchers from University College Dublin used a combination of Pacific Bioscience long-read and Illumina short-read technologies to sequence type strains of Candida krusei and Pichia kudriavzevii. From there, they re-sequenced dozens more clinical and environmental isolates, exploring the relationships between the strains and their genomic diversity.

The team's results, published in PLOS Pathogens today, provided a clearer look at the relationships between these strains and confirmed that the fluconazole drug-resistant, yeast infection-causing C. krusei species and the environmental/food industry species P. kudriavzevii are one and the same. Based on such findings, the authors cautioned that care should be considered when employing P. kudriavzevii in food and other industries, given its potential for drug resistance and human infection.

"If I suggested using drug-resistant Candida albicans to make food, I would be stopped immediately," senior author Kenneth Wolfe, a genomic evolution researcher at the University College Dublin, said in a statement. "But with drug-resistant Candida krusei, nobody bats an eyelid because the food makers use a different name for it."

Although C. albicans yeast account for more than half of invasive yeast infections diagnosed around the world, the team explained, C. krusei can cause infections and is estimated to account for some 2 percent of candidiasis cases. There has been some speculation that C. krusei may overlap with several other yeast species, namely P. kudriavzevii (formerly known as Issatchenkia orientalis) and C. glycerinogenes.

Likewise, an earlier phylogenetic analysis suggested C. krusei falls in the Pichiaceae family and is distantly related to other Candida pathogens, despite its fluconazole resistance and opportunistic pathogenicity.

To explore these relationships further, the researchers used PacBio and Illumina instruments to produce high-quality reference genomes for a C. krusei type strain called CBS573 and the CBS5147 type strain for P. kudriavzevii. After demonstrating that the two strains were 99.6 percent identical at the nucleotide level, they annotated the genomes with the help of RNA sequence data for CBS573, uncovering more than 5,100 protein-coding genes.

The team went on to characterize the P. kudriavzevii/C. krusei genome content and structure, comparing it to the yeast model organism Saccharomyces cerevisiae. It also re-sequenced 30 environmental and clinical isolates of P. kudriavzevii, P. norvegensis, and P. fermentans with Illumina short-read technology.

When the researchers teased out relationships between the strains, based on sequence data for a large yeast gene called MDN1, they saw genetic ties between P. kudriavzevii and P. norvegensis, a strain used for pickling cucumbers. On the other hand, these strains were more distantly related to the strawberry plant pathogen P. membranifaciens, sequenced for a prior study, or the notorious human C. albicans pathogen.

By screening the newly sequenced strains for sensitivity or resistance to four anti-fungal drugs, meanwhile, the team saw fluconazole resistance in all of the P. kudriavzevii strains considered, while documenting a range of sensitivity or resistance profiles for the other drugs. 

"The discovery that clinical and environmental isolates are interspersed in a phylogenetic tree of strains and do not form distinct clades indicates that there is no justification for continuing to use both names for this species," the authors wrote, cautioning that "use of P. kudriavzevii in biotechnology … presents a potential hazard to the health of immunocompromised workers, and potentially also to consumers."

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