Cited by 57Fungal Infections and StudiesFungal and yeast genetics researchEndoplasmic Reticulum Stress and Disease

Eca1, a Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Is Involved in Stress Tolerance and Virulence in Cryptococcus neoformans

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Fan, Weihua, Idnurm, Alexander, Breger, Julia, Mylonakis, Eleftherios, Heitman, Joseph·2007·Infection and Immunity

Abstract

The basidiomycetous fungal pathogen Cryptococcus neoformans is adapted to survive challenges in the soil and environment and within the unique setting of the mammalian host. A C. neoformans mutant was isolated with enhanced virulence in a soil amoeba model that nevertheless exhibits dramatically reduced growth at mammalian body temperature (37°C). This mutant phenotype results from an insertion in the ECA1 gene, which encodes a sarcoplasmic/endoplasmic reticulum (ER) Ca 2+-ATPase (SERCA)-type calcium pump. Infection in murine macrophages, amoebae (Acanthamoeba castellanii), nematodes (Caenorhabditis elegans), and wax moth (Galleria mellonella) larvae revealed that the eca1 mutants are virulent or hypervirulent at permissive growth temperatures but attenuated at 37°C. Deletion mutants lacking the entire ECA1 gene were also hypersensitive to the calcineurin inhibitors cyclosporin and FK506 and to ER and osmotic stresses. An eca1 Δ cna1 Δ mutant lacking both Eca1 and the calcineurin catalytic subunit was more sensitive to high temperature and ER stresses than the single mutants and exhibited reduced survival in C. elegans and attenuated virulence towards wax moth larvae at temperatures that permit normal growth in vitro. Eca1 is likely involved in maintaining ER function, thus contributing to stress tolerance and virulence acting in parallel with Ca 2+-calcineurin signaling.

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  • In C. neoformans, mediators of Ca2+ signaling such as calcineurin, calmodulin, and SERCA are central to maintaining intracellular Ca2+ homeostasis while withstanding host stresses.

    “In C. neoformans mediators of the Ca 2ϩ signaling pathway, such as calcineurin, calmodulin, and the sarco (endo)plasmic reticulum Ca 2ϩ -ATPase are central to maintaining intracellular Ca 2ϩ homeostasis while withstanding the multitude of stresses imposed by the host (33).”

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  1. [15]Casadevall, A., and J. Perfect. 1998. Cryptococcus neoformans. American Society for Microbiology Press, Washington, DC.
  2. [16]Castellani, A. 1930. An amoeba growing in cultures of a yeast: preliminary note. J. Trop. Med. Hyg. 33:160. [Google Scholar]
  3. [32]Fujimura, M., N. Ochiai, M. Oshima, T. Motoyama, A. Ichiishi, R. Usami, K. Horikoshi, and I. Yamaguchi. 2003. Putative homologs of SSK22 MAPKK kinase and PBS2 MAPK kinase of Saccharomyces cerevisiae encoded by os-4 and os-5 genes for osmotic sensitivity and fungicide resistance in Neurospora crassa. Biosci. Biotechnol. Biochem. 67:186-191. [DOI] [PubMed] [Google Scholar]

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Authors
Fan, W., Idnurm, A., Breger, J., Mylonakis, E., & Heitman, J.
Affiliations
  • Duke Medical Center (US)
  • Massachusetts General Hospital (US)
Corresponding author
Heitman, Joseph
Venue
Infection and Immunity
Published
2007-07
Volume
75
Issue
7
Pages
3394-3405
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
OpenAlex
W2171788472
Cited by
57
References
76
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 5 · 2015: 1 · 2014: 3 · 2013: 6 · 2012: 3
FWCI
4.14
Type
journal article
Language
en
Open access
Locations
  • Infection and Immunity (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ellison Medical Foundation
  • National Institute of Allergy and Infectious Diseases (T32AI52080, R01AI042159, AI 042159, K08AI063084, AI063443, R01AI063443, K08AI63084, T32AI052080)
Topics
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
sarco/endoplasmic reticulum Ca2+-ATPase, Cryptococcus neoformans, fungal virulence, stress tolerance, calcineurin signaling, cyclosporine, FK506, endoplasmic reticulum stress, osmotic stress, high temperature sensitivity, Acanthamoeba castellanii, Galleria mellonella, Caenorhabditis elegans, macrophage infection, fungal pathogens
MeSH terms
Calcium-Transporting ATPases, Animals, Cell Line, Cryptococcus neoformans, Endoplasmic Reticulum, Macrophages, Moths, Sarcoplasmic Reticulum, Virulence, Gene Expression Regulation, Fungal, Caenorhabditis elegans, Heat-Shock Response, Acanthamoeba castellanii

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