DNA 结合事件的记录揭示了被重新利用的白色念珠菌调控网络对肠道共生的重要性。
Recording of DNA-binding events reveals the importance of a repurposed Candida albicans regulatory network for gut commensalism.
机构信息
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Cell Host Microbe. 2021 Jun 9;29(6):1002-1013.e9. doi: 10.1016/j.chom.2021.03.019. Epub 2021 Apr 28.
Candida albicans is a fungal component of the human gut microbiota and an opportunistic pathogen. C. albicans transcription factors (TFs), Wor1 and Efg1, are master regulators of an epigenetic switch required for fungal mating that also control colonization of the mammalian gut. We show that additional mating regulators, WOR2, WOR3, WOR4, AHR1, CZF1, and SSN6, also influence gut commensalism. Using Calling Card-seq to record Candida TF DNA-binding events in the host, we examine the role and relationships of these regulators during murine gut colonization. By comparing in-host transcriptomes of regulatory mutants with enhanced versus diminished commensal fitness, we also identify a set of candidate commensalism effectors. These include Cht2, a GPI-linked chitinase whose gene is bound by Wor1, Czf1, and Efg1 in vivo, that we show promotes commensalism. Thus, the network required for a C. albicans sexual switch is biochemically active in the host intestine and repurposed to direct commensalism.
白色念珠菌是人类肠道微生物群的真菌组成部分，也是一种机会性病原体。白色念珠菌转录因子（TFs），Wor1 和 Efg1，是真菌交配所需的表观遗传开关的主要调节因子，也控制着哺乳动物肠道的定植。我们表明，其他交配调节因子，WOR2、WOR3、WOR4、AHR1、CZF1 和 SSN6，也影响肠道共生。使用 Calling Card-seq 在宿主中记录白色念珠菌 TF 的 DNA 结合事件，我们研究了这些调节剂在小鼠肠道定植过程中的作用和关系。通过比较具有增强和减弱共生适应性的调节突变体的体内转录组，我们还确定了一组候选共生效应因子。其中包括 Cht2，一种 GPI 连接的几丁质酶，其基因在体内被 Wor1、Czf1 和 Efg1 结合，我们证明它促进了共生。因此，白色念珠菌性转换所需的网络在宿主肠道中具有生物化学活性，并被重新用于指导共生。
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