Glucose promotes stress resistance in the fungal pathogen Candida albicans.
Metabolic adaptation, and in particular the modulation of carbon assimilatory pathways during disease progression, is thought to contribute to the pathogenicity of Candida albicans. Therefore, we have examined the global impact of glucose upon the C. albicans transcriptome, testing the sensitivity of this pathogen to wide-ranging glucose levels (0.01, 0.1, and 1.0%). We show that, like Saccharomyces cerevisiae, C. albicans is exquisitely sensitive to glucose, regulating central metabolic genes even in response to 0.01% glucose. This indicates that glucose concentrations in the bloodstream (approximate range 0.05-0.1%) have a significant impact upon C. albicans gene regulation. However, in contrast to S. cerevisiae where glucose down-regulates stress responses, some stress genes were induced by glucose in C. albicans. This was reflected in elevated resistance to oxidative and cationic stresses and resistance to an azole antifungal agent. Cap1 and Hog1 probably mediate glucose-enhanced resistance to oxidative stress, but neither is essential for this effect. However, Hog1 is phosphorylated in response to glucose and is essential for glucose-enhanced resistance to cationic stress. The data suggest that, upon entering the bloodstream, C. albicans cells respond to glucose increasing their resistance to the oxidative and cationic stresses central to the armory of immunoprotective phagocytic cells.
Rodaki
Alexandra
A
Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
Bohovych
Iryna M
IM
Enjalbert
Brice
B
Young
Tim
T
Odds
Frank C
FC
Gow
Neil A R
NA
Brown
Alistair J P
AJ
D000935:Antifungal Agents / Q000494:pharmacology; D050976:Basic-Leucine Zipper Transcription Factors; D001786:Blood Glucose / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D002177:Candidiasis / Q000097:blood*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009997:Osmotic Pressure; D018384:Oxidative Stress; D010545:Peroxides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014199:Trehalose / Q000378:metabolism
D000935:Antifungal Agents; D050976:Basic-Leucine Zipper Transcription Factors; D001786:Blood Glucose; C426523:CAP1 protein, Candida albicans; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D010545:Peroxides; D017382:Reactive Oxygen Species; D014199:Trehalose; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose