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Background  Iron is an essential nutrient for almost all organisms, and generating iron limiting conditions for pathogens is one of the host defense strategies against microbial infections. Excess of iron can be toxic; therefore, iron uptake is tightly controlled. The high affinity iron uptake system of the opportunistic pathogenic yeast  Candida albicans  has been shown to be essential for virulence. Several transcription factors and regulators of iron uptake genes were identified, but the knowledge of signaling pathways is still limited. Gene expression profiling of the Δ hog1  deletion mutant indicated an involvement of the mitogen activated protein (MAP) kinase Hog1p. However, the function of Hog1p in the response of  C. albicans  to iron availability was not studied in detail. Thus, we analyzed phenotypic and molecular responses of  C. albicans  to different iron concentrations particularly with respect to the activity of the Hog1p MAP kinase module.    Results  We observed flocculation of yeast cells, when the iron ion concentration was equal to or higher than 5 μM. This phenotype was dependent on the MAP kinase Hog1p and the corresponding MAP kinase kinase Pbs2p. Moreover, high extracellular iron ion concentrations led to hyper-phosphorylation of Hog1p. We determined lower amounts of multicopper ferroxidase (MCFO) proteins and lower ferric reductase activity, when the iron ion concentration in the medium was increased. This effect was also observed for the Δ hog1  mutant. However, the amounts of MCFO proteins and the cell surface ferric reductase activity were increased in the Δ hog1  in comparison to wild type cells. This effect was independent of iron availability in growth media.    Conclusions  In  C. albicans , the MAP kinase Hog1p is part of the network regulating the response of the organism to iron availability. Hog1p was transiently phosphorylated under high iron concentrations and was essential for a flocculent phenotype. Furthermore, deletion of  HOG1  led to increased levels of components of the reductive iron uptake system in comparison to the wild-type, independent of iron concentrations in the media. However, the additional induction of this system by low iron concentrations was independent of  HOG1.

Involvement of the mitogen activated protein kinase Hog1p in the response of Candida albicansto iron availability