Expansion of the TLO gene family enhances the virulence of Candida species

PloS One
Peter R FlanaganDerek J Sullivan

Abstract

The TLO genes are a family of subtelomeric ORFs in the fungal pathogens Candida albicans and C. dubliniensis encoding a subunit of the Mediator complex homologous to Med2. The more virulent pathogen C. albicans has 15 copies of the gene whereas the less pathogenic species C. dubliniensis has only two. To investigate if expansion of the TLO repertoire in C. dubliniensis has an effect on phenotype and virulence we expressed three representative C. albicans TLO genes (TLOβ2, TLOγ11 and TLOα12) in a wild type C. dubliniensis background, under the control of either their native or the ACT1 promoter. Expression of TLOβ2 resulted in a hyperfilamentous phenotype, while overexpression of TLOγ11 and TLOα12 resulted in enhanced resistance to oxidative stress. Expression of all three TLO genes from the ACT1 promoter resulted in increased virulence in the Galleria infection model. In order to further investigate if individual TLO genes exhibit differences in function we expressed six representative C. albicans TLO genes in a C. dubliniensis Δtlo1/Δtlo2 double mutant. Differences were observed in the ability of the expressed CaTLOs to complement the various phenotypes of the mutant. All TLO genes with the exception of TLOγ7 could restore fil...Continue Reading

References

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Citations

Jan 15, 2019·Current Genetics·Gary P MoranDerek J Sullivan
Mar 22, 2020·Current Opinion in Genetics & Development·Erin Henninger, Maria T Teixeira
Mar 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Sheena D Singh-BabakAlexander D Johnson
Aug 27, 2021·Frontiers in Genetics·Mostafa RahnamaMark L Farman

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Methods Mentioned

BETA
PCR
environmental stress

Software Mentioned

Prism GraphPad
GeneWiz
GraphPad Prism
Excel
Mediator

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