Using in vivo transcriptomics and RNA enrichment to identify genes involved in virulence of Candida glabrata

ABSTRACT

Candida species are the most commonly isolated opportunistic fungal pathogens in humans. Candida albicans causes most of the diagnosed infections, closely followed by Candida glabrata. C. albicans is well studied, and many genes have been shown to be important for infection and colonization of the host. It is however less clear how C. glabrata infects the host. With the help of fungal RNA enrichment, we here investigated for the first time the transcriptomic profile of C. glabrata during urinary tract infection (UTI) in mice. In the UTI model, bladders and kidneys are major target organs and therefore fungal transcriptomes were addressed in these organs. Our results showed that, next to adhesins and proteases, nitrogen metabolism and regulation play a vital role during C. glabrata UTI. Genes involved in nitrogen metabolism were upregulated and among them we show that DUR1,2 (urea amidolyase) and GAP1 (amino acid permease) were important for virulence. Furthermore, we confirmed the importance of the glyoxylate cycle in the host and identified MLS1 (malate synthase) as an important gene necessary for C. glabrata virulence. In conclusion, our study shows with the support of in vivo transcriptomics how C. glabrata adapts to host conditions.

KEYWORDS:

• Candida glabrata
• urinary tract infection
• transcriptomics
• bioluminescence
• mice
• virulence

Acknowledgement

Authors are thankful to Danielle Brandalise for excellent technical assistance. Authors acknowledge the laboratory of Bernhard Hube for providing strains used in this study. Authors thanks collaborators of the Lausanne Genomic Technology Facility (LGTF) for technical help. This work was supported by a grant of the Swiss National Research Foundation grant 31003A_172958 to DS.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author’s contributions

SS designed and performed experiments and contributed to writing, ED and VDT contributed to analysis, DS designed experiments and contributed to writing.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2022.2095716

Additional information

Funding

The authors reported there is no funding associated with the work featured in this article.