Candida albicans developmental regulation: adenylyl cyclase as a coincidence detector of parallel signals

In the healthy individual, Candida albicans is frequently found as a harmless commensal residing in the gastrointestinal tract. However, in the compromised patient, C. albicans may invade the body and cause disease that is associated with poor prognosis and high mortality. The C. albicans adenylyl cyclase, Cyr1, which is required for virulence in animal models, regulates three developmental programs, including invasive filamentous growth, phenotypic switching to a mating-competent cell type, and biofilm formation. Evidence suggests that Cyr1 controls these phenotypes in response to various environmental cues that are present within microbial populations. Additionally, C. albicans secretes an autoregulatory molecule, farnesol, which was recently shown to directly inhibit Cyr1 activity. Below, we summarize recent advances in our understanding of Cyr1-regulated development and discuss the multiple inputs known to positively and negatively regulate cAMP synthesis. We discuss the possibility that Cyr1 acts as a coincidence detector that tightly regulates fungal development in response to parallel environmental stimuli, and highlight ways in which this might occur.

► Adenylyl cyclase (Cyr1) regulates developmental processes such as hyphal growth, biofilm formation, and phenotypic switching.
► Cyr1 activity is stimulated directly by regulatory proteins (Ras1 and Gpa2), peptidoglycan fragments and carbon dioxide.
► Farnesol, an autoregulatory molecule secreted by C. albicans, inhibits Cyr1 activity.