A MAP kinase pathway is implicated in the pseudohyphal induction by hydrogen peroxide in Candica albicans.

Abstract

Hydrogen peroxide (H(2)O(2)) functions as a ubiquitous intracellular messenger besides as an oxidative stress molecule. This dual role is based on the distinct cellular responses against different concentrations of H(2)O(2). Previously, we demonstrated that both low (> 1 mM) and high (4-10 mM) doses of exogenous H(2)O(2) induce filamentous growth with distinct cell morphology and growth rate in Candida albicans, suggesting the different transcription response. In this study, we revealed that the sub-toxic and toxic levels of H(2)O(2) indeed induced pseudohyphae, but not true hyphae. Supporting this, several hyphae-specific genes that are expressed in true hyphae induced by serum were not detected in either sub-toxic or toxic H(2)O(2) condition. A DNA microarray analysis was conducted to reveal the transcription profiles in cells treated with sub-toxic and toxic conditions of H(2)O(2). Under the sub-toxic condition, a small number of genes involved in cell proliferation and metabolism were up-regulated, whereas a large number of genes were up-regulated in the toxic condition where the genes required for growth and proliferation were selectively restricted. For pseudohyphal induction by sub-toxic H(2)O(2), Cek1 MAPK activating the transcription factor Cph1 was shown to be important. The absence of expression of several hyphae-specific genes known to be downstream targets of Cph1-signaling pathway for true hyphae formation suggests that the Cek1-mediated signaling pathway is not solely responsible for pseudohyphal formation by subtoxic H(2)O(2) and, but instead, complex networking pathway may exists by the activation of different regulators.