Ras Signaling Gets Fine-Tuned: Regulation of Multiple Pathogenic Traits of Candida albicans

Candida albicans is an opportunistic fungal pathogen that can cause disseminated infection in patients with indwelling cathe-ters or other implanted medical devices. A common resident of the humanmicrobiome, C. albicans responds to environmental signals, such as cell contact with catheter materials and exposure to serum or CO2, by triggering the expression of a variety of traits, some of which are known to contribute to its pathogenic lifestyle. Such traits include adhesion, biofilm formation, fila-mentation, white-to-opaque (W-O) switching, and two recently described phenotypes, finger and tentacle formation. Under dis-tinct sets of environmental conditions and in specific cell types (mating type-like a [MTLa]/alpha cells, MTL homozygotes, or daughter cells), C. albicans utilizes (or reutilizes) a single signal transduction pathway—the Ras pathway—to affect these phe-notypes. Ras1, Cyr1, Tpk2, and Pde2, the proteins of the Ras signaling pathway, are the only nontranscriptional regulatory pro-teins that are known to be essential for regulating all of these processes. How does C. albicans utilize this one pathway to regu-late all of these phenotypes? The regulation of distinct and yet related processes by a single, evolutionarily conserved pathway is accomplished through the use of downstream transcription factors that are active under specific environmental conditions and in different cell types. In this minireview, we discuss the role of Ras signaling pathway components and Ras pathway-regulated transcription factors as well as the transcriptional regulatory networks that fine-tune gene expression in diverse biological con-texts to generate specific phenotypes that impact the virulence of C. albicans. Candida albicans is a common commensal microbe of the gas-trointestinal and female reproductive tracts, but it can be