The lack of upstream elements of the Cek1 and Hog1 mediated pathways leads to a synthetic lethal phenotype upon osmotic stress in Candida albicans.

Different signal transduction pathways mediated by MAP kinases have been described in Candida albicans. These pathways sense different stimuli and, therefore, elaborate specific responses. Hog1 was identified as the MAPK that is primarily involved in stress response and virulence, while Cek1 was more specific to cell wall biogenesis, mating and biofilm formation. In the present work, mutants defective in both pathways have been characterized under osmotic stress. Both routes are required for a full response against high osmotic challenge, since mutants defective in both pathways displayed aberrant morphology, cell polarity defects and abnormal chitin deposition, which correlate with loss of viability and appearance of apoptotic markers. These alterations occurred in spite of proper Hog1 and Cek1 phosphorylation and increased intra-cellular glycerol accumulation. The relevance of both routes in virulence is shown as ssk1 msb2 sho1 opy2 mutants are avirulent in a mouse systemic model of infection and display reduced virulence in the Galleria mellonella model.