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Candida albicans Cek1 mitogen-activated protein kinase signaling enhances fungicidal activity of salivary histatin 5. - PubMed - NCBI
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Antimicrob Agents Chemother. 2015;59(6):3460-8. doi: 10.1128/AAC.00214-15. Epub 2015 Mar 30.

Candida albicans Cek1 mitogen-activated protein kinase signaling enhances fungicidal activity of salivary histatin 5.

Author information

1
Department of Oral Biology, University at Buffalo, Buffalo, New York, USA.
2
Department of Biological Sciences, University at Buffalo, Buffalo, New York, USA.
3
Department of Oral Biology, University at Buffalo, Buffalo, New York, USA edgerto@buffalo.edu.

Abstract

Candida albicans is a major etiological organism for oropharyngeal candidiasis (OPC), while salivary histatin 5 (Hst 5) is a human fungicidal protein that protects the oral cavity from OPC. C. albicans senses its environment by mitogen-activated protein kinase (MAPK) activation that can also modulate the activity of some antifungal drugs, including Hst 5. We found that phosphorylation of the MAPK Cek1, induced either by N-acetylglucosamine (GlcNAc) or serum, or its constitutive activation by deletion of its phosphatase Cpp1 elevated the susceptibility of C. albicans cells to Hst 5. Cek1 phosphorylation but not hyphal formation was needed for increased Hst 5 sensitivity. Interference with the Cek1 pathway by deletion of its head sensor proteins, Msb2 and Sho1, or by addition of secreted aspartyl protease (SAP) cleavage inhibitors, such as pepstatin A, reduced Hst 5 susceptibility under Cek1-inducing conditions. Changes in fungal cell surface glycostructures also modulated Hst 5 sensitivity, and Cek1-inducing conditions resulted in a higher uptake rate of Hst 5. These results show that there is a consistent relationship between activation of Cek1 MAPK and increased Hst 5 susceptibility in C. albicans.

PMID:
25824232
PMCID:
PMC4432120
DOI:
10.1128/AAC.00214-15
[Indexed for MEDLINE]
Free PMC Article
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