The adaptive metabolic response involves specific protein glutathionylation during the filamentation process in the pathogen Candida albicans

ABSTRACT: Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to the systemic disease candidiasis. Its ability to adopt various morphological forms, such as unicellular yeasts, filamentous pseudohyphae and hyphae, contributes to its ability to survive within the host. It has been suggested that the antioxidant glutathione is involved in the filamentation process. We investigated S-glutathionylation, the reversible binding of glutathione to proteins, and the functional consequences on C. albicans metabolic remodeling during the yeast-to-hyphae transition. Our work provided evidence for the specific glutathionylation of mitochondrial proteins involved in bioenergetics pathways in filamentous forms and a regulation of the main enzyme of the glyoxylate cycle, isocitrate lyase, by glutathionylation. Our proteomic data demonstrate that the binding of one glutathione molecule to isocitrate lyase in the hyphal forms leads to enzyme inactivation which was reversed by glutaredoxin treatment. We also assessed the effect of alternative carbon sources on glutathione levels and isocitrate lyase activity. Changes in nutrient availability led to morphological flexibility and was related to perturbations in glutathione levels and isocitrate lyase activity, confirming the key role of the maintenance of intracellular redox status in the adaptive metabolic strategy of the pathogen.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Candida Albicans (yeast)

TISSUE(S): Cell Culture, Vegetative Cell (sensu Fungi)

SUBMITTER: Camille GARCIA  

LAB HEAD: Jean-Michel Camadro

PROVIDER: PXD003685 | Pride | 2016-04-21

REPOSITORIES: Pride