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Molecular and Cellular Biology, July 2000, p. 4635-4647, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Dominant Active Alleles of RIM101 (PRR2) Bypass the pH Restriction on Filamentation of Candida albicans

Abdelmalic El Barkani,1 Oliver Kurzai,1 William A. Fonzi,2 Ana Ramon,2 Amalia Porta,2,3 Matthias Frosch,1 and Fritz A. Mühlschlegel1,*

Institut für Hygiene und Mikrobiologie, Universität Würzburg, 97080 Würzburg, Germany1; Department of Microbiology and Immunology, School of Medicine, Georgetown University Medical Center, Washington, D.C. 20007-21972; and International Institute of Genetics and Biophysics, 80125 Naples, Italy3

Received 29 November 1999/Returned for modification 13 January 2000/Accepted 11 April 2000

Morphological development of the fungal pathogen Candida albicans is profoundly affected by ambient pH. Acidic pH restricts growth to the yeast form, whereas neutral pH permits development of the filamentous form. Superimposed on the pH restriction is a temperature requirement of approximately 37°C for filamentation. The role of pH in development was investigated by selecting revertants of phr2Delta mutants that had gained the ability to grow at acid pH. The extragenic suppressors in two independent revertants were identified as nonsense mutations in the pH response regulator RIM101 (PRR2) that resulted in a carboxy-terminal truncation of the open reading frame. These dominant active alleles conferred the ability to filament at acidic pH, to express PHR1, an alkaline-expressed gene, at acidic pH, and to repress the acid-expressed gene PHR2. It was also observed that both the wild-type and mutant alleles could act as multicopy suppressors of the temperature restriction on filamentation, allowing extensive filamentation at 29°C. The ability of the activated alleles to promote filamentation was dependent upon the developmental regulator EFG1. The results suggest that RIM101 is responsible for the pH dependence of hyphal development.

* Corresponding author. Mailing address: Institut für Hygiene und Mikrobiologie, Universität Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. Phone: 49-931-201-3901. Fax: 49-931-201-3445. E-mail: fmuehlschlegel{at}hygiene.uni-wuerzburg.de.

Molecular and Cellular Biology, July 2000, p. 4635-4647, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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