Faculty Collaboration Database

Candida albicans SET1 encodes a histone 3 lysine 4 methyltransferase that contributes to the pathogenesis of invasive candidiasis. Mol Microbiol 2006 May;60(3):697-709

Date

04/25/2006

Pubmed ID

16629671

DOI

10.1111/j.1365-2958.2006.05121.x

Scopus ID

2-s2.0-33645835480 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

Candida albicans causes diverse mucosal and systemic diseases. Although this versatility likely depends upon carefully co-ordinated gene expression, epigenetic regulation in C. albicans remains poorly characterized. Screening a genomic expression library, we identified C. albicans Set1p as an immunogenic protein with homology to a lysine histone methyltransferase of Saccharomyces cerevisiae. In this study, we demonstrated that total immunoglobulin, IgG and IgM titers against a unique Set1p N-terminal fragment were significantly higher among patients with disseminated candidiasis (DC) or oropharyngeal candidiasis than controls. Disruption of SET1 resulted in complete loss of methylation of histone 3 at lysine residue 4, hyperfilamentous growth under embedded conditions, less negative cell surface charges and diminished adherence to epithelial cells, effects that were reversed upon gene re-insertion at a disrupted locus. During murine DC, the null mutant was associated with prolonged survival and lower tissue burdens. Taken together, our findings suggest that SET1 regulates multiple processes important to the pathogenesis of candidiasis. The Set1p N-terminal fragment does not exhibit significant homology to eukaryotic or microbial proteins, and might represent a novel therapeutic, preventive or diagnostic target.

Author List

Raman SB, Nguyen MH, Zhang Z, Cheng S, Jia HY, Weisner N, Iczkowski K, Clancy CJ

MESH terms used to index this publication - Major topics in bold

Animals
Candida albicans
Candidiasis
Candidiasis, Oral
DNA-Binding Proteins
Fungal Proteins
HT29 Cells
Histone-Lysine N-Methyltransferase
Humans
Male
Mice
Mice, Inbred ICR
Saccharomyces cerevisiae Proteins
Transcription Factors
Virulence