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Eukaryotic Cell, April 2009, p. 627-639, Vol. 8, No. 4
1535-9778/09/$08.00+0     doi:10.1128/EC.00246-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Candida albicans RFX2 Encodes a DNA Binding Protein Involved in DNA Damage Responses, Morphogenesis, and Virulence{triangledown}

Binghua Hao,1,{dagger} Cornelius J. Clancy,1,2,{dagger} Shaoji Cheng,1 Suresh B. Raman,1 Kenneth A. Iczkowski,3 and M. Hong Nguyen1*

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania,1 VA Pittsburgh Health System, Pittsburgh, Pennsylvania,2 Department of Pathology, University of Colorado, Denver, Colorado3

Received 23 July 2008/ Accepted 28 January 2009

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.

* Corresponding author. Mailing address: University of Pittsburgh, 3550 Terrace Street, Suite 871, Pittsburgh, PA 15203. Phone: (412) 383-5193. Fax: (412) 648-8455. E-mail: MHN5+{at}pitt.edu

{triangledown} Published ahead of print on 27 February 2009.

{dagger} Contributed equally to the study.

Eukaryotic Cell, April 2009, p. 627-639, Vol. 8, No. 4
1535-9778/09/$08.00+0     doi:10.1128/EC.00246-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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