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ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model

Gastrointestinal colonization by Candida species is considered the main source of candidemia. The ERG3 gene in Candida albicans encodes a sterol C5,6-desaturase, which is essential for ergosterol biosynthesis. Although ERG3 inactivation shows reduced virulence in mouse models of disseminated candidi...

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Autores principales: Hirayama, Tatsuro, Miyazaki, Taiga, Sumiyoshi, Makoto, Ashizawa, Nobuyuki, Takazono, Takahiro, Yamamoto, Kazuko, Imamura, Yoshifumi, Izumikawa, Koichi, Yanagihara, Katsunori, Kohno, Shigeru, Mukae, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823479/
https://www.ncbi.nlm.nih.gov/pubmed/33396406
http://dx.doi.org/10.3390/pathogens10010023
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author Hirayama, Tatsuro
Miyazaki, Taiga
Sumiyoshi, Makoto
Ashizawa, Nobuyuki
Takazono, Takahiro
Yamamoto, Kazuko
Imamura, Yoshifumi
Izumikawa, Koichi
Yanagihara, Katsunori
Kohno, Shigeru
Mukae, Hiroshi
author_facet Hirayama, Tatsuro
Miyazaki, Taiga
Sumiyoshi, Makoto
Ashizawa, Nobuyuki
Takazono, Takahiro
Yamamoto, Kazuko
Imamura, Yoshifumi
Izumikawa, Koichi
Yanagihara, Katsunori
Kohno, Shigeru
Mukae, Hiroshi
author_sort Hirayama, Tatsuro
collection PubMed
description Gastrointestinal colonization by Candida species is considered the main source of candidemia. The ERG3 gene in Candida albicans encodes a sterol C5,6-desaturase, which is essential for ergosterol biosynthesis. Although ERG3 inactivation shows reduced virulence in mouse models of disseminated candidiasis, the role of ERG3 in intestinal infections is unknown. Here, we infected mice with the C. albicans strains CAE3DU3 and CAF2-1, containing mutant and wild-type ERG3, respectively, and studied gut infection and colonization by these strains. We found that the CAE3DU3 strain showed reduced colonization, pathogenesis, damage to gut mucosa, and chemokine production in the mouse model of invasive candidiasis. Additionally, mice inoculated with CAE3DU3 showed lower mortality than mice inoculated with CAF2-1 (p < 0.0001). Chemokines were less induced in the gut inoculated with CAE3DU3 than in the gut inoculated with CAF2-1. Histopathologically, although the wild-type gene was associated with a higher pathogenicity and invasion of the gut mucosa and liver tissues causing remarkable tissue necrosis, the erg3/erg3 mutant was associated with a higher accumulation of cells and lower damage to surrounding tissues than wild-type ERG3. These results establish that the ergosterol biosynthetic pathway may be associated with C. albicans gut colonization and subsequent dissemination.
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spelling pubmed-78234792021-01-24 ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model Hirayama, Tatsuro Miyazaki, Taiga Sumiyoshi, Makoto Ashizawa, Nobuyuki Takazono, Takahiro Yamamoto, Kazuko Imamura, Yoshifumi Izumikawa, Koichi Yanagihara, Katsunori Kohno, Shigeru Mukae, Hiroshi Pathogens Article Gastrointestinal colonization by Candida species is considered the main source of candidemia. The ERG3 gene in Candida albicans encodes a sterol C5,6-desaturase, which is essential for ergosterol biosynthesis. Although ERG3 inactivation shows reduced virulence in mouse models of disseminated candidiasis, the role of ERG3 in intestinal infections is unknown. Here, we infected mice with the C. albicans strains CAE3DU3 and CAF2-1, containing mutant and wild-type ERG3, respectively, and studied gut infection and colonization by these strains. We found that the CAE3DU3 strain showed reduced colonization, pathogenesis, damage to gut mucosa, and chemokine production in the mouse model of invasive candidiasis. Additionally, mice inoculated with CAE3DU3 showed lower mortality than mice inoculated with CAF2-1 (p < 0.0001). Chemokines were less induced in the gut inoculated with CAE3DU3 than in the gut inoculated with CAF2-1. Histopathologically, although the wild-type gene was associated with a higher pathogenicity and invasion of the gut mucosa and liver tissues causing remarkable tissue necrosis, the erg3/erg3 mutant was associated with a higher accumulation of cells and lower damage to surrounding tissues than wild-type ERG3. These results establish that the ergosterol biosynthetic pathway may be associated with C. albicans gut colonization and subsequent dissemination. MDPI 2020-12-31 /pmc/articles/PMC7823479/ /pubmed/33396406 http://dx.doi.org/10.3390/pathogens10010023 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hirayama, Tatsuro
Miyazaki, Taiga
Sumiyoshi, Makoto
Ashizawa, Nobuyuki
Takazono, Takahiro
Yamamoto, Kazuko
Imamura, Yoshifumi
Izumikawa, Koichi
Yanagihara, Katsunori
Kohno, Shigeru
Mukae, Hiroshi
ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model
title ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model
title_full ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model
title_fullStr ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model
title_full_unstemmed ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model
title_short ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model
title_sort erg3-encoding sterol c5,6-desaturase in candida albicans is required for virulence in an enterically infected invasive candidiasis mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823479/
https://www.ncbi.nlm.nih.gov/pubmed/33396406
http://dx.doi.org/10.3390/pathogens10010023
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