Fungal biotin homeostasis is essential for immune evasion after macrophage phagocytosis and virulence.,Cellular Microbiology

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Fungal biotin homeostasis is essential for immune evasion after macrophage phagocytosis and virulence.
Cellular Microbiology ( IF 2.6 ) Pub Date : 2020-02-21 , DOI: 10.1111/cmi.13197
Marcel Sprenger ₁ , Teresa S Hartung ₁ , Stefanie Allert ₁ , Stephanie Wisgott ₁ , Maria J Niemiec _{2,

3} , Katja Graf ₁ , Ilse D Jacobsen _{2,

3,

4} , Lydia Kasper ₁ , Bernhard Hube _{1,

4}

Affiliation

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.

中文翻译：

真菌生物素稳态对于巨噬细胞吞噬作用和毒力后的免疫逃避至关重要。

生物素是中枢代谢过程中多种酶的重要辅助因子。虽然许多细菌和大多数真菌能合成生物素从头，念珠菌属。对这种维生素是营养缺陷的，因此需要有效的摄取系统以促进感染过程中生物素的获取。在这里，我们显示了光滑念珠菌和白色念珠菌使用了高度保守的系统来吸收和调节生物素，其中包括高亲和力生物素转运蛋白Vht1和转录因子Vhr1。在体外生物素耗尽和巨噬细胞吞噬后，这两个物种均诱导生物素代谢基因的表达，表明念珠菌中的生物素水平较低。含有吞噬体。与此相符，我们观察到预先缺乏生物素的念珠菌细胞和缺乏VHR1或VHT1基因的缺失突变体的细胞内增殖减少。VHT1对于全身性白色念珠菌在小鼠全身感染时的全部毒力至关重要，缺乏VHT1可以减少感染了光滑念珠菌的大脑和感染白色念珠菌的大脑和肾脏的真菌负担。总之，我们的数据表明，Vht1介导的生物素获取对于光滑念珠菌和白色念珠菌至关重要。在巨噬细胞和全身感染的细胞内生长过程中。

更新日期：2020-02-21

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