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. 2006 Feb;5(2):347-58.
doi: 10.1128/EC.5.2.347-358.2006.

The Cek1 and Hog1 mitogen-activated protein kinases play complementary roles in cell wall biogenesis and chlamydospore formation in the fungal pathogen Candida albicans

B Eisman  1 , R Alonso-Monge, E Román, D Arana, C Nombela, J Pla
Affiliations

The Cek1 and Hog1 mitogen-activated protein kinases play complementary roles in cell wall biogenesis and chlamydospore formation in the fungal pathogen Candida albicans

B Eisman et al. Eukaryot Cell. 2006 Feb.

Abstract

The Hog1 mitogen-activated protein (MAP) kinase mediates an adaptive response to both osmotic and oxidative stress in the fungal pathogen Candida albicans. This protein also participates in two distinct morphogenetic processes, namely the yeast-to-hypha transition (as a repressor) and chlamydospore formation (as an inducer). We show here that repression of filamentous growth occurs both under serum limitation and under other partially inducing conditions, such as low temperature, low pH, or nitrogen starvation. To understand the relationship of the HOG pathway to other MAP kinase cascades that also play a role in morphological transitions, we have constructed and characterized a set of double mutants in which we deleted both the HOG1 gene and other signaling elements (the CST20, CLA4, and HST7 kinases, the CPH1 and EFG1 transcription factors, and the CPP1 protein phosphatase). We also show that Hog1 prevents the yeast-to-hypha switch independent of all the elements analyzed and that the inability of the hog1 mutants to form chlamydospores is suppressed when additional elements of the CEK1 pathway (CST20 or HST7) are altered. Finally, we report that Hog1 represses the activation of the Cek1 MAP kinase under basal conditions and that Cek1 activation correlates with resistance to certain cell wall inhibitors (such as Congo red), demonstrating a role for this pathway in cell wall biogenesis.

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Figures

FIG. 1.
FIG. 1.
Morphological transition of hog1 mutant under different conditions. C. albicans strains were inoculated to 105 cells/ml into Lee's medium or minimal medium at different pHs and incubated at 37°C (A) or liquid YPD supplemented with 5% serum and incubated at 24, 30, or 37°C (B). Microphotographs were taken after 3 h of incubation. Bars, 10 μm. wt, wild type.
FIG. 2.
FIG. 2.
MAP kinase activation and cell morphologies. (A) Ten milliliters of cell cultures growing exponentially (1 OD) was taken and processed for immunoblot assay. The same membrane was incubated subsequently with the antibodies (Ab) indicated. Ab p42-44 P, phospho-p42/44 MAP kinase; Ab Hog1, ScHog1 polyclonal antibody; Ab Cek1, Ab-CaCek1; Cek1*, Cek1 phosphorylated. (B) Cell morphology of different mutants under subinducing conditions. Cells were inoculated at 106 cells/ml in YPD plus 5% serum or serum and incubated at 30°C for 5 h before being photographed. Bars, 10 μm. wt, wild type.
FIG. 3.
FIG. 3.
Filamentation of hog1, cph1, and efg1 mutants. Cells were inoculated at 106 cells/ml in YPD, YPD plus 5% serum, or 100% serum and incubated at 30°C. Photomicrographs were taken after 5 h of incubation. Bars, 10 μm. wt, wild type.
FIG. 4.
FIG. 4.
Chlamydospore formation. CFU (25 to 50) were spread onto cornmeal agar and incubated in darkness at 24°C for 72 h. wt, wild type.
FIG. 5.
FIG. 5.
Influence of EFG1 overexpression on chlamydospore formation. Wild-type and hog1 mutant strains were transformed either with (+) the plasmid pRC2312P-H (which consists of the EFG1 gene under the control of PCK1 promoter) or the vector. The transformants obtained were spread onto cornmeal agar and incubated in darkness for 72 h before photographs were taken. The arrow points to an offset wider field of the hog1 mutant carrying the EFG1-overexpressing plasmid. wt, wild type.
FIG. 6.
FIG. 6.
Susceptibility to osmotic stress. Tenfold serial dilutions from exponentially growing cultures were spotted on YPD plates supplemented or not (control) with the osmotic agents indicated and incubated at 37°C for 24 h. wt, wild type.
FIG. 7.
FIG. 7.
Growth in the presence of cell wall-disturbing compounds. Serial dilutions of cells were spotted on plates supplemented with calcofluor white or Congo red, and plates were incubated at 37°C for 24 h before photographs were taken. wt, wild type.
FIG. 8.
FIG. 8.
Congo red effect on Cek1 phosphorylation and growth. Stationary-phase cells were diluted at 0.1 OD in YPD supplemented with Congo red at 0, 100, 200, and 300 μg/ml. Samples were collected after 1 and 2 h of growth at 37°C and processed for Cek1 phosphorylation by Western blotting analysis (A) or growth measurement (B). wt, wild type; Cek1*, Cek1 phosphorylated.
FIG. 9.
FIG. 9.
Susceptibility to Zymolyase. The strains indicated, PAKs and MAP kinases (A) or phosphatases and transcription factors (B), were grown overnight at 37°C in the presence of different amounts of Zymolyase starting with an OD of 0.025. Growth is depicted as the percentage of growth in YPD supplemented with Zymolyase compared to growth in YPD alone. wt, wild type.
FIG. 10.
FIG. 10.
Proposed model of interaction between the pathways mediated by Hog1 and Cek1 MAP kinases. Osmotic stress triggers Hog1 activation through both branches, enabling the cell to adapt to hyperosmotic conditions (black arrow). The Cek1 pathway is involved in the construction of the cell wall (gray arrow); the stimulus is not known and is depicted as a question mark. Regarding morphogenesis, the HOG pathway plays an inhibitory role over yeast-to-hypha transition; this role is independent or dominant over the CEK1 pathway (discontinuous black bar) and the transcription factor, Efg1. Under specific conditions, such as low glucose concentration, darkness, low temperature (24°C to 28°C), and microaerophilia, Hog1 plays an inducing role in the formation of chlamydospores; this positive role may be played, presumably, through Cst20, Ste11, Hst7, and Cek1 (discontinuous thick gray arrow). Under standard growth conditions, Hog1 controls the activation of Cek1 (light gray bar).
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