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Candida albicans RFX2 encodes a DNA binding protein involved in DNA damage responses, morphogenesis, and virulence. Eukaryot Cell 2009 Apr;8(4):627-39

Date

03/03/2009

Pubmed ID

19252121

Pubmed Central ID

PMC2669197

DOI

10.1128/EC.00246-08

Scopus ID

2-s2.0-64749106541   25 Citations

Abstract

We previously showed that Candida albicans orf19.4590, which we have renamed RFX2, expresses a protein that is reactive with antibodies in persons with candidiasis. In this study, we demonstrate that C. albicans RFX2 shares some functional redundancy with Saccharomyces cerevisiae RFX1. Complementation of an S. cerevisiae rfx1 mutant with C. albicans RFX2 partially restored UV susceptibility and the repression of DNA damage response genes. DNA damage- and UV-induced genes RAD6 and DDR48 were derepressed in a C. albicans rfx2 null mutant strain under basal conditions, and the mutant was significantly more resistant to UV irradiation, heat shock, and ethanol than wild-type strain SC5314. The rfx2 mutant was hyperfilamentous on solid media and constitutively expressed hypha-specific genes HWP1, ALS3, HYR1, ECE1, and CEK1. The mutant also demonstrated increased invasion of solid agar and significantly increased adherence to human buccal epithelial cells. During hematogenously disseminated candidiasis, mice infected with the mutant had a significantly delayed time to death compared to the wild type. During oropharyngeal candidiasis, mice infected with the mutant had significantly lower tissue burdens in the oral cavity and esophagus at 7 days and they were less likely to develop disseminated infections because of mucosal translocation. The data demonstrate that C. albicans Rfx2p regulates DNA damage responses, morphogenesis, and virulence.

Author List

Hao B, Clancy CJ, Cheng S, Raman SB, Iczkowski KA, Nguyen MH

Author

Kenneth A. Iczkowski MD Professor in the Pathology department at Medical College of Wisconsin




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

Animals
Candida albicans
Candidiasis
DNA Damage
DNA-Binding Proteins
Fungal Proteins
Gene Expression Regulation, Fungal
Humans
Male
Mice
Mice, Inbred ICR
Mutation
Ultraviolet Rays
Virulence
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc