title: Ppg1, a PP2A-type protein phosphatase, controls filament extension and virulence in Candida albicans.
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 ppg1Δ/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.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Mohammad T
authors.initials: MT
authors.lastname: Albataineh
authors.affiliation: Department of Biology and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lazzell
authors.affiliation: Department of Biology and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Lopez-Ribot
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA kadosh@uthscsa.edu.
authors.forename: David
authors.initials: D
authors.lastname: Kadosh
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000166:cytology / Q000201:enzymology* / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology*; D020134:Catalytic Domain; D015536:Down-Regulation; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry / Q000502:physiology*; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D008807:Mice, Inbred BALB C; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D020890:Neuregulin-1; D054648:Protein Phosphatase 2