Adaptation of Candida albicans to growth on sorbose via monosomy of chromosome 5 accompanied by duplication of another chromosome carrying a gene responsible for sorbose utilization.
Candida albicans, a fungus that normally inhabits the digestive tract and other mucosal surfaces, can become a pathogen in immunocompromised individuals, causing severe or even fatal infection. Mechanisms by which C. albicans can evade commonly used antifungal agents are not fully understood. We are studying a model system involving growth of C. albicans on toxic sugar sorbose, which represses synthesis of cell wall glucan and, as a result, kills fungi in a manner similar to drugs from the echinocandins class. Adaptation to sorbose occurs predominantly due to reversible loss of one homolog of chromosome 5 (Ch5), which results in upregulation of the metabolic gene SOU1 (SOrbose Utilization) on Ch4. Here, we show that growth on sorbose due to Ch5 monosomy can involve a facultative trisomy of a hybrid Ch4/7 that serves to increase copy number of the SOU1 gene. This shows that control of expression of SOU1 can involve multiple mechanisms; in this case, negative regulation and increase in gene copy number operating simultaneously in cell.
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, USA.
Anatoliy
A
Kravets
Feng
F
Yang
Gabor
G
Bethlendy
Yongbing
Y
Cao
Fred
F
Sherman
Elena
E
Rustchenko
D000220:Adaptation, Biological; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D015825:Chromosomes, Fungal; D015966:Gene Expression Regulation, Fungal; D009006:Monosomy; D013013:Sorbose / Q000378:metabolism* / Q000633:toxicity*; D014314:Trisomy
D013013:Sorbose
aneuploidy; regulation; resistance