Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783639845331009536 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7823479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hirayamatatsuro erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT miyazakitaiga erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT sumiyoshimakoto erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT ashizawanobuyuki erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT takazonotakahiro erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT yamamotokazuko erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT imamurayoshifumi erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT izumikawakoichi erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT yanagiharakatsunori erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT kohnoshigeru erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel AT mukaehiroshi erg3encodingsterolc56desaturaseincandidaalbicansisrequiredforvirulenceinanentericallyinfectedinvasivecandidiasismousemodel |