Fungal biotin homeostasis is essential for immune evasion after macrophage phagocytosis and virulence.
Animals
Biotin
/ genetics
Brain
/ microbiology
Candida
/ genetics
Candida albicans
/ genetics
Candida glabrata
/ genetics
Homeostasis
Immune Evasion
Kidney
/ microbiology
Macrophages
/ microbiology
Mice
Mice, Inbred BALB C
Phagocytosis
/ immunology
Phagosomes
/ microbiology
Symporters
/ genetics
Transcription Factors
/ metabolism
Virulence
/ genetics
Candida albicans
Candida glabrata
biotin
macrophage
metabolism
virulence
Journal
Cellular microbiology
ISSN: 1462-5822
Titre abrégé: Cell Microbiol
Pays: India
ID NLM: 100883691
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
19
07
2019
revised:
05
02
2020
accepted:
10
02
2020
pubmed:
23
2
2020
medline:
2
6
2021
entrez:
22
2
2020
Statut:
ppublish
Résumé
Biotin is an important cofactor for multiple enzymes in central metabolic processes. While many bacteria and most fungi are able to synthesise biotin de novo, Candida spp. are auxotrophic for this vitamin and thus require efficient uptake systems to facilitate biotin acquisition during infection. Here we show that Candida glabrata and Candida albicans use a largely conserved system for biotin uptake and regulation, consisting of the high-affinity biotin transporter Vht1 and the transcription factor Vhr1. Both species induce expression of biotin-metabolic genes upon in vitro biotin depletion and following phagocytosis by macrophages, indicating low biotin levels in the Candida-containing phagosome. In line with this, we observed reduced intracellular proliferation of both Candida cells pre-starved of biotin and deletion mutants lacking VHR1 or VHT1 genes. VHT1 was essential for the full virulence of C. albicans during systemic mouse infections, and the lack of VHT1 led to reduced fungal burden in C. glabrata-infected brains and C. albicans-infected brains and kidneys. Together, our data suggest a critical role of Vht1-mediated biotin acquisition for C. glabrata and C. albicans during intracellular growth in macrophages and systemic infections.
Substances chimiques
Symporters
0
Transcription Factors
0
Biotin
6SO6U10H04
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13197Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2020 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.
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