ROLE OF SIR2 IN C. ALBICANS STRESS SURVIVAL

Candida albicans is an opportunistic pathogen and resistance to fungistatic drug such as Fluconazole is increasing in prevalence. Sirtuins or Sir2 family of proteins, are NAD+ dependent histone deacetylases of lysine residues. In a previous study, we demonstrated that Saccharomyces cerevisiae Sir2 coordinates a network of stress responses (Nussbaum et al 2014, Weindling and Bar-Nun 2015). Another study performed in Berman lab showed that C. albicans Sir2 increases noise in gene expression at telomeres due to silencing (Anderson et al 2014). Intriguingly, my preliminary results suggest that Sir2 reduces the variability of the survival and growth in drug in an epigenetic manner. In addition, we observed that cells lacking Sir2 are more sensitive to drug and to heat-shock stresses. The goal of my current work is to determine how Sir2 regulates a diverse range of stress responses, from obvious effects on chromatin that appear to facilitate bet-hedging behaviors at the telomeres, to effects on drug and elevated temperature responses that appear to buffer phenotypic variability. The way(s) by which Sir2 affects the ability of C. albicans cells to survive in different physiological stresses and thus may contribute to the recurrence of infections suggests that CaSir2 may be a “master regulator” of stress response.