The adaptive response to alternative carbon sources in the pathogen Candida albicans involves a remodeling of thiol- and glutathione-dependent redox status

Candida albicans is an opportunist pathogen responsible for a large spectrum of infec-tions, from superficial mycosis to systemic diseases known as candidiasis. During infec-tion in vivo, Candida albicans must adapt to host microenvironments and this adaptive response is crucial for the survival of this organism, as it facilitates the effective assimila-tion of alternative carbon sources others than glucose. We performed a global proteomic analysis on the global changes in protein abundance in response to changes in micronu-trient levels, and, in parallel, explored changes in the intracellular redox and metabolic status of the cells. We show here that each of the carbon sources considered - glucose, acetate and lactate - induces a unique pattern of response in C. albicans cells, and that some conditions trigger an original and specific adaptive response involving the adapta-tion of metabolic pathways, but also a complete remodeling of thiol-dependent antioxi-dant defenses. Protein S-thiolation and the overproduction of reduced glutathione are two components of the response to high glucose concentration. In the presence of acetate, glutathione-dependent oxidative stress occurs, reduced thiol groups bind to pro-teins, and glutathione is exported out of the cells, these changes probably being trig-gered by an increase in glutathione-S-transferases. Overall, our results suggest that the role of cellular redox status regulation and defenses against oxidative stress, including the thiol-and glutathione-dependent response, in the adaptive response of C. albicans to alternative carbon sources should be reconsidered.

Automated summary

Candida albicans adapts to host microenvironments by remodeling metabolic pathways and antioxidant defenses in response to changes in carbon sources. Glucose, acetate, and lactate induce unique patterns of response in C. albicans cells. The role of cellular redox status regulation and defenses against oxidative stress, including thiol-and glutathione-dependent response, in the adaptive response of C. albicans to alternative carbon sources should be reconsidered.