Fungal biotin homeostasis is essential for immune evasion after macrophage phagocytosis and virulence. (7th March 2020)

• Record Type: Journal Article
• Authors: Sprenger, Marcel; Hartung, Teresa S.; Allert, Stefanie; Wisgott, Stephanie; Niemiec, Maria J.; Graf, Katja; Jacobsen, Ilse D.; Kasper, Lydia; Hube, Bernhard
• Is Part Of: Cellular microbiology. Volume 22:Number 7(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-07
• Subjects: biotin -- Candida albicans -- Candida glabrata -- macrophage -- metabolism -- virulence; Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.13197
• Languages: English
• ISSNs: 1462-5814

Abstract

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. Abstract : The vitamin biotin is essential for all organisms, including the opportunistic fungal pathogens Candida albicans and C. glabrata . Both species are auxotrophic for this vitamin and acquire host biotin during infection by using a conserved system, consisting of the biotin transporter Vht1 and the transcriptional regulator Vhr1. We show that Vht1‐mediated biotin acquisition is critical for both species during intracellular proliferation within and escape from macrophages, and systemic infections. We conclude that biotin access is limited in phagosomes containing fungi.