ABSTRACT
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 of
C. albicans
filamentous growth signal transduction pathways, considerably little is known about the role of phosphatases. Here we demonstrate that
PPG1
, encoding a putative type 2A-related protein phosphatase, is important for
C. albicans
filament extension, invasion, and virulence in a mouse model of systemic candidiasis.
PPG1
is also important for downregulation of
NRG1
, a key transcriptional repressor of
C. albicans
filamentous growth, and is shown to affect the expression of several filament-specific target genes. An epistasis analysis suggests that
PPG1
controls
C. albicans
filamentation via the cyclic AMP-protein kinase A (cAMP-PKA) signaling pathway. We demonstrate that Ppg1 possesses phosphatase activity and that a
ppg1
catalytic mutant shows nearly equivalent filamentation, invasion, and virulence defects compared to those of a
ppg1
Δ/Δ strain. Overall, our results suggest that phosphatases, such as Ppg1, play critical roles in controlling and fine-tuning
C. albicans
filament extension and virulence as well as signal transduction pathways, transcriptional regulators, and target genes associated with these processes.