Trabajo presentado en la 11º Reunión de la Red Española de Levaduras, celebrada en El Escorial (España), del 13 al 15 de diciembre de 2017
The interaction of Candida albicans with the innate immune system is the key determinant of the pathogen/commensal balance. Upon phagocytosis, C. albicans adapts to the nutrient conditions within the phagosome by inducing alternative metabolic pathways, such amino acids uptake as a carbon source. The metabolism of these nutrients is essential for neutralization of the macrophage phagosome, a process that contributes to hyphal growth and fungal escape from the phagocyte. When C. albicans utilizes amino acids as the sole carbon source, it excretes ammonia raising the pH of the phagosome. This process depends on Stp2, a transcription factor that controls expression of amino acid permeases Pga1and Pga2. In C. albicans, The NDR signalling mediated by the Cbk1 kinase is required for hyphal growth and biofilm formation. Here we uncovered a new function of Cbk1 in neutralization of extracellular pH. Mutants lacking CBK1 were defective in alkalinization on amino-acid-rich medium and showed differences in post-translational modifications of Stp2 compared with wild-type cells. In addition, the hypomorpic cbk1-6A mutant showed reduced macrophage cytotoxicity. RNA seq of phagocytated cbk1-6A cells is in progress.
MICINN/European Union FEDER (BIO2015-70195-C2-2R) y Ayudas a Grupos de Investigación de la Junta de Extremadura (GR15008).