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Research Article | Molecular Biology and Physiology

The Vacuolar Ca2+ ATPase Pump Pmc1p Is Required for Candida albicans Pathogenesis

Arturo Luna-Tapia, Christian DeJarnette, Emily Sansevere, Parker Reitler, Arielle Butts, Kirk E. Hevener, Glen E. Palmer
Aaron P. Mitchell, Editor
Arturo Luna-Tapia
Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Christian DeJarnette
Department of Molecular Immunology and Biochemistry, College of Graduate Health Sciences, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Emily Sansevere
Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Parker Reitler
Department of Molecular Immunology and Biochemistry, College of Graduate Health Sciences, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Arielle Butts
Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Kirk E. Hevener
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Glen E. Palmer
Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Aaron P. Mitchell
Carnegie Mellon University
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DOI: 10.1128/mSphere.00715-18
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ABSTRACT

Calcium is a critically important secondary messenger of intracellular signal transduction in eukaryotes but must be maintained at low levels in the cytoplasm of resting cells to avoid toxicity. This is achieved by several pumps that actively transport excess cytoplasmic Ca2+ out of the cell across the plasma membrane and into other intracellular compartments. In fungi, the vacuole serves as the major storage site for excess Ca2+, with two systems actively transporting cytoplasmic calcium ions into the vacuole. The H+/Ca2+ exchanger, Vcx1p, harnesses the proton-motive force across the vacuolar membrane (generated by the V-ATPase) to drive Ca2+ transport, while the P-type ATPase Pmc1p uses ATP hydrolysis to translocate Ca2+ into the vacuole. Ca2+-dependent signaling is required for the prevalent human fungal pathogen Candida albicans to endure exposure to the azole antifungals and to cause disease within the mammalian host. The purpose of this study was to determine if the Pmc1p or Vcx1p Ca2+ pumps are required for C. albicans pathogenicity and if these pumps impact antifungal resistance. Our results indicate that Pmc1p is required by C. albicans to transition from yeast to hyphal growth, to form biofilms in vitro, and to cause disease in a mouse model of disseminated infection. Moreover, loss of Pmc1p function appears to enhance C. albicans azole tolerance in a temperature-dependent manner.

IMPORTANCE Maintenance of Ca2+ homeostasis is important for fungal cells to respond to a multitude of stresses, as well as antifungal treatment, and for virulence in animal models. Here, we demonstrate that a P-type ATPase, Pmc1p, is required for Candida albicans to respond to a variety of stresses, affects azole susceptibility, and is required to sustain tissue invasive hyphal growth and to cause disease in a mouse model of disseminated infection. Defining the mechanisms responsible for maintaining proper Ca2+ homeostasis in this important human pathogen can ultimately provide opportunities to devise new chemotherapeutic interventions that dysregulate intracellular signaling and induce Ca2+ toxicity.

  • Copyright © 2019 Luna-Tapia et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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The Vacuolar Ca2+ ATPase Pump Pmc1p Is Required for Candida albicans Pathogenesis
Arturo Luna-Tapia, Christian DeJarnette, Emily Sansevere, Parker Reitler, Arielle Butts, Kirk E. Hevener, Glen E. Palmer
mSphere Feb 2019, 4 (1) e00715-18; DOI: 10.1128/mSphere.00715-18

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The Vacuolar Ca2+ ATPase Pump Pmc1p Is Required for Candida albicans Pathogenesis
Arturo Luna-Tapia, Christian DeJarnette, Emily Sansevere, Parker Reitler, Arielle Butts, Kirk E. Hevener, Glen E. Palmer
mSphere Feb 2019, 4 (1) e00715-18; DOI: 10.1128/mSphere.00715-18
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KEYWORDS

Candida albicans
Pmc1p
Vcx1p
calcium
pathogenesis
vacuole

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