Candida albicans Is Resistant to Polyglutamine Aggregation and Toxicity.
Disruption of protein quality control can be detrimental, having toxic effects on single cell organisms and contributing to neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's in humans. Here, we examined the effects of polyglutamine (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 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.
Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, AB25 2ZD, UK.|Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada.
Michelle D
MD
Leach
Banting and Best Department of Medical Research, The Donnelly Centre, University of Toronto, Ontario, M5S 3E1, Canada.|Department of Computer Science, University of Toronto, Ontario M5S 2E4, Canada.
TaeHyung
T
Kim
Department of Pathology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Sonja E
SE
DiGregorio
Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada.
Cathy
C
Collins
Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada.|Banting and Best Department of Medical Research, The Donnelly Centre, University of Toronto, Ontario, M5S 3E1, Canada.
Zhaolei
Z
Zhang
Department of Pathology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada Martin.Duennwald@schulich.uwo.ca leah.cowen@utoronto.ca.
Martin L
ML
Duennwald
Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada Martin.Duennwald@schulich.uwo.ca leah.cowen@utoronto.ca.
Leah E
LE
Cowen
D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D002177:Candidiasis / Q000235:genetics / Q000382:microbiology; D002352:Carrier Proteins / Q000235:genetics; D019295:Computational Biology; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D010455:Peptides / Q000378:metabolism* / Q000633:toxicity; D020543:Proteome / Q000235:genetics*; D040901:Proteomics / Q000379:methods; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
D002352:Carrier Proteins; D050956:HSP40 Heat-Shock Proteins; D010455:Peptides; D020543:Proteome; C070320:SIS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C520576:Sgt2 protein, S cerevisiae; C097188:polyglutamine
Aggregation; Candida albicans; PolyQ; Saccharomyces cerevisiae; Toxicity