Ppg1, a PP2A-Type Protein Phosphatase, Controls Filament Extension and Virulence in Candida albicans

Candida albicans , a major human fungal pathogen, is the primary cause of invasive candidiasis in a wide array of immunocompromised patients.C. albicans virulence requires the ability to undergo a reversible morphological transition from yeast to filaments in response to a variety of host environmental cues. These cues are sensed by the pathogen and activate multiple signal transduction pathways to induce filamentation. Reversible phosphorylation events are critical for regulation of many of these pathways. While a variety of protein kinases are known to function as components ofC. albicans filamentous growth signal transduction pathways, considerably little is known about the role of phosphatases. Here we demonstrate thatPPG1 , encoding a putative type 2A-related protein phosphatase, is important forC. albicans filament extension, invasion, and virulence in a mouse model of systemic candidiasis.PPG1 is also important for downregulation ofNRG1 , a key transcriptional repressor ofC. albicans filamentous growth, and is shown to affect the expression of several filament-specific target genes. An epistasis analysis suggests thatPPG1 controlsC. albicans filamentation via the cyclic AMP-protein kinase A (cAMP-PKA) signaling pathway. We demonstrate that Ppg1 possesses phosphatase activity and that appg1 catalytic mutant shows nearly equivalent filamentation, invasion, and virulence defects compared to those of appg1 Δ/Δ strain. Overall, our results suggest that phosphatases, such as Ppg1, play critical roles in controlling and fine-tuningC. albicans filament extension and virulence as well as signal transduction pathways, transcriptional regulators, and target genes associated with these processes.