Transcriptomic analysis reveals global and temporal transcription changes during Candida glabrata adaptation to an oxidative environment.

ABSTRACT

The ability to survive host-elicited oxidative stress is critical for microbial pathogens to cause infection. The human fungal pathogen C.glabrata can tolerate high levels of oxidative stress and proliferate inside phagocytes. Previous studies had successfully identified a transcription response to oxidative stress including induction of a core set of detoxification genes. However, the findings only represent an early snapshot of a highly dynamic process lacking temporal resolution. Here, we compare the transcriptome of C. glabrata at various points after exposure to hydrogen peroxide in order to study its adaptation to an oxidative environment. Our results reveal global and temporal gene expression changes during an immediate response; up-regulating genes related to peroxide detoxification, while down-regulating genes essential for growth. As cells adapt to the oxidative environment, a dramatic transcriptome reprogramming occurred to restore key cellular functions, protein homeostasis and biosynthesis of trehalose, carbohydrate, fatty acid and ergosterol. Interestingly, biofilm and drug transporter genes as well as many genes implicated in virulence, were induced during the adaptation stage. Our finding, therefore, suggests a role of oxidative stress adaptation in promoting virulence and drug resistance traits of C. glabrata during infection.