Candida albicans Is Resistant to Polyglutamine Aggregation and Toxicity

Michelle D Leach, TaeHyung Kim, Sonja E DiGregorio, Cathy Collins, Zhaolei Zhang, Martin L Duennwald, Leah E Cowen

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Abstract

Disruption of protein quality control can be detrimental, having toxic effects on single cell organisms, contributing to neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's in humans. Here we examined the effects of polyQ aggregation in a major fungal pathogen of humans, Candida albicans, with the goal of identifying new approaches to disable this fungus. However, we discovered that expression of poly-glutamine (polyQ) stretches up to 230Q had no effect on C. albicans ability to grow and withstand proteotoxic stress. Bioinformatics analysis demonstrates that C. albicans has a similarly glutamine rich proteome to the unicellular fungus Saccharomyces cerevisiae, which exhibits polyQ toxicity with as few as 72Q. Surprisingly, global transcriptional profiles indicated no significant change upon induction of up to 230Q. Proteomic analysis highlighted two key interactors of 230Q, Sis1 and Sgt2, however, loss of either protein had no additional effect on C. albicans toxicity. Our data suggest that C. albicans has evolved powerful mechanisms to overcome the toxicity associated with aggregation-prone proteins, providing a unique model for studying polyQ associated diseases.

Original languageEnglish
Pages (from-to)95-108
Number of pages14
JournalG3: Genes, Genomes, Genetics Mission
Volume7
Issue number1
Early online date2 Nov 2016
DOIs
Publication statusPublished - 1 Jan 2017

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Keywords

  • Candida albicans
  • genomics
  • polyglutamine
  • aggragation
  • stress response
  • toxicity
  • polyq
  • Saccharomyces cerevisiae

Cite this

Leach, M. D., Kim, T., DiGregorio, S. E., Collins, C., Zhang, Z., Duennwald, M. L., & Cowen, L. E. (2017). Candida albicans Is Resistant to Polyglutamine Aggregation and Toxicity. G3: Genes, Genomes, Genetics Mission, 7(1), 95-108. https://doi.org/10.1534/g3.116.035675