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Infection and Immunity, October 2000, p. 5953-5959, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Candida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions

Dana Davis,1,* John E. Edwards Jr.,2,3 Aaron P. Mitchell,1 and Ashraf S. Ibrahim2,3

Department of Microbiology, Columbia University, New York, New York 100321; Harbor-UCLA Research and Education Institute, Torrance, California 905022; and Department of Medicine, UCLA School of Medicine, Los Angeles, California 900243

Received 11 April 2000/Returned for modification 15 June 2000/Accepted 5 July 2000

The ability of Candida albicans to respond to diverse environments is critical for its success as a pathogen. The RIM101 pathway controls gene expression and the yeast-to-hyphal transition in C. albicans in response to changes in environmental pH in vitro. In this study, we found that the RIM101 pathway is necessary in vivo for pathogenesis. First, we show that rim101-/rim101- and rim8-/rim8- mutants have a significant reduction in virulence using the mouse model of hematogenously disseminated systemic candidiasis. Second, these mutants show a marked reduction in kidney pathology. Third, the rim101-/rim101- and rim8-/rim8- mutants show defects in the ability to damage endothelial cells in situ. Finally, we show that an activated allele of RIM101, RIM101-405, is a suppressor of the rim8- mutation in vivo as it rescues the virulence, histological, and endothelial damage defects of the rim8-/rim8- mutant. These results demonstrate that the RIM101 pathway is required for C. albicans virulence in vivo and that the function of Rim8p in pathogenesis is to activate Rim101p.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University, 701 W. 168th St. HHSC Room 918, New York, NY 10032. Phone: (212) 305-1554. Fax: (212) 305-1741. E-mail: dd251{at}columbia.edu.

Infection and Immunity, October 2000, p. 5953-5959, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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