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

M-32 Meeting room 9 MAR 20173 PM

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

 

 Mohammad Al Bataineh, M.D., Ph.D, Assistant Professor

Department of Clinical Sciences

College of Medicine

University of Sharjah

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 PPG 1, 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 Ppgl possesses phosphatase activity and that a ppgl catalytic mutant shows nearly equivalent filamentation, invasion, and virulence defects compared to those of a ppg1∆/∆ . strain. Overall, our results suggest that phosphatases, such as Ppgl, 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.



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