Differential filamentation of Candida albicans and C. dubliniensis is governed by nutrient regulation of UME6 expression

Abstract

Candida dubliniensis is closely related to C. albicans, however it is responsible for fewer infections in humans and is less virulent in animal models of infection. C. dubliniensis forms fewer hyphae in vivo and this may contribute to its reduced virulence. In this study we show that unlike C. albicans, C. dubliniensis fails to form hyphae in YPD supplemented with 10% (v/v) fetal calf serum (YPDS). However, C. dubliniensis filaments in water plus 10% (v/v) fetal calf serum (WS), and this filamentation is inhibited by the addition of peptone and glucose. Repression of filamentation in YPDS could be partly overcome by preculture in synthetic Lee’s medium. Unlike C. albicans, inoculation of C. dubliniensis in YPDS did not result in increased UME6 transcription. However, >100-fold induction of UME6 was observed when C. dubliniensis was inoculated in nutrient poor WS medium. Addition of increasing concentrations of peptone to WS had a dose dependent effect on reducing UME6 expression. Transcript profiling of C. dubliniensis hyphae in WS identified a starvation resposne involving expression of genes in the glyoxylate cycle and fatty acid oxidation. In addition a core, shared transcriptional response with C. albicans could be identified, including expression of virulence-associated genes including SAP456, SAP7, HWP1 and SOD5. Preculture in nutrient limiting medium enhanced adherence of C. dubliniensis, epithelial invasion and survival following co-culture with murine macrophages. In conclusion, C. albicans unlike C. dubliniensis, appears to form hyphae in liquid medium regardless of nutrient availability, which may account for its increased capacity to cause disease in humans.