Rfg1, a Protein Related to the Saccharomyces cerevisiae Hypoxic Regulator Rox1, Controls Filamentous Growth and Virulence in Candida albicans

Abstract

Candida albicans, the major fungal pathogen in humans, can undergo a reversible transition from ellipsoidal single cells (blastospores) to filaments composed of elongated cells attached end to end. This transition is thought to allow for rapid colonization of host tissues, facilitating the spread of infection. Here, we report the identification of Rfg1, a transcriptional regulator that controls filamentous growth of C. albicans in an environment-dependent manner. Rfg1 is important for virulence ofC. albicans in a mouse model and is shown to control a number of genes that have been implicated in this process. The closest relative to Rfg1 in Saccharomyces cerevisiae is Rox1, a key repressor of hypoxic genes. However, Rfg1 does not appear to play a role in the regulation of hypoxic genes in C. albicans. These results demonstrate that a regulatory protein that controls the hypoxic response in S. cerevisiae controls filamentous growth and virulence in C. albicans. The observations described in this paper raise new and intriguing questions about the evolutionary relationship between these processes.

ACKNOWLEDGMENTS

We thank J. Pla, G. Fink, B. Braun, A. Uhl, D. Inglis, and C. Hull for plasmids, strains, primers, and probes and R. Khalaf and R. Zitomer for communicating results prior to publication. We are especially grateful to D. Inglis for assistance in carrying out the virulence experiments. We thank members of the Johnson laboratory for fruitful discussions during the course of the experiments. Sequence data for C. albicans were obtained from the Stanford DNA Sequencing and Technology Center website athttp://www-sequence.stanford.edu/group/candida.

Sequencing of C. albicans was accomplished with the support of the NIDR and the Burroughs Wellcome Fund. This work was supported by the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation Fellowship, DRG-1512, to D.K. and by National Institutes of Health grant GM-37049 to A.D.J.