Candida albicans Commensalism and Pathogenicity Are Intertwined Traits Directed by a Tightly Knit Transcriptional Regulatory Circuit

Abstract

Author SummaryOur skin and mouth, as well as our genital and gastrointestinal tracts, are laden with microorganisms belonging to all three domains of life (bacteria, archaea, and eukaryotes). Much of the time these commensal microorganisms are not only harmless but provide advantages to us. However, when the host's defenses are compromised, some members of the normal flora, such as the fungus C. albicans, can cross the host's protective barriers and colonize virtually every internal organ causing life-threatening conditions. The environment found in the bloodstream and internal organs is presumably distinct from the mucosal surfaces where our flora typically resides. Whether opportunistic pathogens such as C. albicans rely on common or separate gene repertoires to thrive in each of these locales is largely unknown. To address this question we carried out genetic screens in mouse models that recapitulate niches where C. albicans thrives and used genome-wide experimental approaches to uncover the genes required to proliferate in each environment. In fact, the ability of C. albicans to colonize disparate niches within a mammalian host relies on a large, integrated circuit. Our observations suggest that at least some key gene circuits are not dedicated to one niche or another. Rather, thriving in various locales of the host seems to involve the complex regulation of multiple processes, which may allow C. albicans to adjust to different environments.