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Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex.

Publication ,  Journal Article
Jung, K-W; Lee, K-T; Averette, AF; Hoy, MJ; Everitt, J; Heitman, J; Bahn, Y-S
Published in: Sci Rep
May 25, 2018

The unfolded protein response (UPR) pathway, consisting of the evolutionarily conserved Ire1 kinase/endonuclease and the bZIP transcription factor Hxl1, is critical for the pathogenicity of Cryptococcus neoformans; however, its role remains unknown in other pathogenic Cryptococcus species. Here, we investigated the role of the UPR pathway in C. deuterogattii, which causes pneumonia and systemic cryptococcosis, even in immunocompetent individuals. In response to ER stress, C. deuterogattii Ire1 triggers unconventional splicing of HXL1 to induce the expression of UPR target genes such as KAR2, DER1, ALG7, and ERG29. Furthermore, C. deuterogattii Ire1 is required for growth at mammalian body temperature, similar to C. neoformans Ire1. However, deletion of HXL1 does not significantly affect the growth of C. deuterogattii at 37 °C, which is in contrast to the indispensable role of HXL1 in the growth of C. neoformans at 37 °C. Nevertheless, both C. deuterogattii ire1Δ and hxl1Δ mutants are avirulent in a murine model of systemic cryptococcosis, suggesting that a non-thermotolerance phenotypic trait also contributes to the role of the UPR pathway in the virulence of pathogenic Cryptococcus species. In conclusion, the UPR pathway plays redundant and distinct roles in the virulence of members of the pathogenic Cryptococcus species complex.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

May 25, 2018

Volume

8

Issue

1

Start / End Page

8132

Location

England

Related Subject Headings

  • Virulence
  • Unfolded Protein Response
  • Melanins
  • Fungal Proteins
  • Evolution, Molecular
  • Endoplasmic Reticulum Stress
  • Drug Resistance, Fungal
  • Cryptococcus
  • Body Temperature
  • Animals
 

Citation

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MLA
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Jung, K.-W., Lee, K.-T., Averette, A. F., Hoy, M. J., Everitt, J., Heitman, J., & Bahn, Y.-S. (2018). Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex. Sci Rep, 8(1), 8132. https://doi.org/10.1038/s41598-018-26405-5
Jung, Kwang-Woo, Kyung-Tae Lee, Anna F. Averette, Michael J. Hoy, Jeffrey Everitt, Joseph Heitman, and Yong-Sun Bahn. “Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex.Sci Rep 8, no. 1 (May 25, 2018): 8132. https://doi.org/10.1038/s41598-018-26405-5.
Jung K-W, Lee K-T, Averette AF, Hoy MJ, Everitt J, Heitman J, et al. Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex. Sci Rep. 2018 May 25;8(1):8132.
Jung, Kwang-Woo, et al. “Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex.Sci Rep, vol. 8, no. 1, May 2018, p. 8132. Pubmed, doi:10.1038/s41598-018-26405-5.
Jung K-W, Lee K-T, Averette AF, Hoy MJ, Everitt J, Heitman J, Bahn Y-S. Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex. Sci Rep. 2018 May 25;8(1):8132.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

May 25, 2018

Volume

8

Issue

1

Start / End Page

8132

Location

England

Related Subject Headings

  • Virulence
  • Unfolded Protein Response
  • Melanins
  • Fungal Proteins
  • Evolution, Molecular
  • Endoplasmic Reticulum Stress
  • Drug Resistance, Fungal
  • Cryptococcus
  • Body Temperature
  • Animals