A MAP kinase pathway is implicated in the pseudohyphal induction by hydrogen peroxide in Candica albicans
Hydrogen peroxide (H2O2) 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 H2O2. Previously, we demonstrated that both low (> 1 mM) and high (4–10 mM) doses of exogenous H2O2 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 H2O2 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 H2O2 condition. A DNA microarray analysis was conducted to reveal the transcription profiles in cells treated with sub-toxic and toxic conditions of H2O2. 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 H2O2, 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 H2O2 and, but instead, complex networking pathway may exists by the activation of different regulators.
KeywordsCandida albicans H2O2 intracellular messenger signaling pathway transcription profiling
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- Andaluz, E., Ciudad, T., Gomez-Raja, J., Calderone, R., and Larriba, G. (2006). Rad52 depletion in Candida albicans triggers both the DNA-damage checkpoint and filamentation accompanied by but independent of expression of hypha-specific genes. Mol. Microbiol. 59, 1452–1472.PubMedCrossRefGoogle Scholar
- Boisnard, S., Ruprich-Robert, G., Florent, M., Da Silva, B., Chapeland-Leclerc, F., and Papon, N. (2008). Role of Sho1p adaptor in the pseudohyphal development, drugs sensitivity, osmotolerance and oxidant stress adaptation in the opportunistic yeast Candida lusitaniae. Yeast 25, 849–859.PubMedCrossRefGoogle Scholar
- Leberer, E., Harcus, D., Broadbent, I.D., Clark, K.L., Dignard, D., Ziegelbauer, K., Schmidt, A., Gow, N.A., Brown, A.J., and Thomas, D.Y. (1996). Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. Proc. Natl. Acad. Sci. USA 93, 13217–13222.PubMedCrossRefGoogle Scholar
- Li, J., Stouffs, M., Serrander, L., Banfi, B., Bettiol, E., Charnay, Y., Steger, K., Krause, K.H., and Jaconi, M.E. (2006). The NADPH oxidase NOX4 drives cardiac differentiation: Role in regulating cardiac transcription factors and MAP kinase activation. Mol. Biol. Cell. 17, 3978–3988.PubMedCrossRefGoogle Scholar
- Lo, H.J., Kohler, J.R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A., and Fink, G.R. (1997). Nonfilamentous C. albicans mutants are avirulent. Cell 90, 939–949.Google Scholar
- Mesquita, F.S., Dyer, S.N., Heinrich, D.A., Bulun, S.E., Marsh, E.E., and Nowak, R.A. (2009). Reactive oxygen species mediate mitogenic growth factor signaling pathways in human leiomyoma smooth muscle cells. Biol. Reprod. 2009.Google Scholar
- Murad, A.M., d’Enfert, C., Gaillardin, C., Tournu, H., Tekaia, F., Talibi, D., Marechal. D., Marchais, V., Cottin, J., and Brown A.J. (2001a). Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1. Mol. Microbiol. 42, 981–993.PubMedCrossRefGoogle Scholar
- Nantel, A., Dignard, D., Bachewich, C., Harcus, D., Marcil, A., Bouin, A.P., Sensen, C.W., Hogues, H., van het Hoog., M., Gordon, P., et al. (2002). Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition. Mol. Biol. Cell. 13, 3452–3465.PubMedCrossRefGoogle Scholar
- Quinn, J., Findlay, V.J., Dawson, K., Millar, J.B., Jones, N., Morgan, B.A., and Toone, W.M. (2002). Distinct regulatory proteins control the graded transcriptional response to increasing H(2)O(2) levels in fission yeast Schizosaccharomyces pombe. Mol. Biol. Cell. 13, 805–816.PubMedCrossRefGoogle Scholar
- Rhee, S.G., Bae, Y.S., Lee, S.R., and Kwon, J. (2000). Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci. STKE 2000; PE1.Google Scholar
- Rocha, C.R., Schroppel, K., Harcus, D., Marcil, A., Dignard, D., Taylor, B.N., Thomas, D.Y., Whiteway, M., and Leberer, E. (2001). Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans. Mol. Biol. Cell 12, 631–643.Google Scholar
- Sambrook, J., and Russell, D.W. (2001). Molecular cloning: a laboratory manual. (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press).Google Scholar