1. Fungal biotin homeostasis is essential for immune evasion after macrophage phagocytosis and virulence.
- Author
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Sprenger M, Hartung TS, Allert S, Wisgott S, Niemiec MJ, Graf K, Jacobsen ID, Kasper L, and Hube B
- Subjects
- Animals, Biotin genetics, Brain microbiology, Candida genetics, Candida growth & development, Candida pathogenicity, Candida albicans genetics, Candida glabrata genetics, Kidney microbiology, Mice, Mice, Inbred BALB C, Phagosomes microbiology, Symporters genetics, Transcription Factors metabolism, Virulence genetics, Biotin metabolism, Candida metabolism, Homeostasis, Immune Evasion, Macrophages microbiology, Phagocytosis immunology
- Abstract
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., (© 2020 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.)
- Published
- 2020
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