Histatin 5 Initiates Osmotic Stress Response in Candida albicans via Activation of the Hog1 Mitogen-Activated Protein Kinase Pathway

Department of Oral Biology, SUNY at Buffalo Main Street Campus, Buffalo, NY 14214, USA.
Eukaryotic Cell (Impact Factor: 3.18). 11/2007; 6(10):1876-88. DOI: 10.1128/EC.00039-07
Source: PubMed


Histatin 5 (Hst 5) is a salivary cationic peptide that has toxicity for Candida albicans by inducing rapid cellular ion imbalance and cell volume loss. Microarray analyses of peptide-treated cells were used to
evaluate global gene responses elicited by Hst 5. The major transcriptional response of C. albicans to Hst 5 was expression of genes involved in adaptation to osmotic stress, including production of glycerol (RHR2, SKO1, and PDC11) and the general stress response (CTA1 and HSP70). The oxidative-stress genes AHP1, TRX1, and GPX1 were mildly induced by Hst 5. Cell defense against Hst 5 was dependent on the Hog1 mitogen-activated protein kinase (MAPK)
pathway, since C. albicans hog1/hog1 mutants were significantly hypersensitive to Hst 5 but not to Mkc1 MAPK or Cek1 MAPK mutants. Activation of the high-osmolarity
glycerol (HOG) pathway was demonstrated by phosphorylation of Hog1 MAPK as well as by glycerol production following Hst 5
treatment in a dose-dependent manner. C. albicans cells prestressed with sorbitol were less sensitive to subsequent Hst 5 treatment; however, cells treated concurrently with
osmotic stress and Hst 5 were hypersensitive to Hst 5. In contrast, cells subjected to oxidative stress had no difference
in sensitivity to Hst 5. These results suggest a common underlying cellular response to osmotic stress and Hst 5. The HOG
stress response pathway likely represents a significant and effective challenge to physiological levels of Hst 5 and other
toxic peptides in fungal cells.

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Available from: Slavena Vylkova, Jan 27, 2015
    • "The killing of C. albicans is accompanied by the release of intracellular potassium ions, and the TRK1 potassium channel is critical (Pollock et al., 1984; Xu et al., 1999; Baev et al., 2004). Histatins inhibit respiration and induce the formation of reactive oxygen species in C. albicans cells (Helmerhorst et al., 2001) and induce an osmotic stress response (Vylkova et al., 2007). "
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    • "Further studies are necessary to clarify the roles of Bcr1 and Ssd1 in early versus late mechanisms of resistance to AMPs. The Hog1 (high osmolarity glycerol) MAPK pathway, which provides a response to osmotic, oxidative, and heavy-metal exposure stresses in fungal cells, was shown to be activated in the presence of AMPs, such as NaD1, HBD2, HBD3, and histatin-5 (a salivary cationic AMP that has a role in keeping C. albicans in its commensal state; Yeaman et al., 1996; Vylkova et al., 2007; Argimon et al., 2011; Hayes et al., 2013). The injuries imposed on C. albicans by these defensins seem to share common features with osmotic and/or oxidative stress (Argimon et al., 2011). "
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