Multiplexed functional metagenomic analysis of the infant microbiome identifies effectors of NF-κB, autophagy, and cellular redox state.
Multiplexed functional metagenomic analysis of the infant microbiome identifies effectors of NF-κB, autophagy, and cellular redox state.
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DOI：
10.1016/j.celrep.2021.109746
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发表时间：
2021-09-21
期刊：
影响因子：
8.8
通讯作者：
Brady SF
中科院分区：
文献类型：
--
作者：
Piscotta FJ;Whitfield ST;Nakashige TG;Estrela AB;Ali T;Brady SF
人体微生物区系对宿主健康起着至关重要的作用。婴儿微生物组的适当发育尤其重要。它的生物失调既会导致短期的健康问题，也会导致持续到成年的长期疾病。微生物群与宿主相互作用的一个中心方式是通过产生效应器分子，如蛋白质和小分子。在这里，我们分析了一个由14个婴儿粪便微生物群构建的元基因组文库，以产生调节三种不同宿主途径的效应物：免疫反应(核因子κB[NF-κB]激活)、自噬(Lc3-B点状形成)和氧化还原电位(NADH/NAD比率)。我们鉴定了微生物组编码的生物活性代谢物，包括康能达胺和硫化氢及其相关的生物合成基因，以及来自克雷伯氏菌的一个以前未鉴定的自噬诱导操纵子。这项工作扩大了我们对影响宿主途径的微生物效应分子的理解。元基因组文库的平行功能筛选可以很容易地扩展到研究其他宿主过程。婴儿粪便超基因组文库的构建宿主细胞过程细菌效应物的多重筛选微生物组编码效应物的鉴定肺炎克雷伯氏菌操纵子诱导自噬的产物硫化氢和卡本达胺等人。从14个婴儿粪便微生物组构建的超基因组文库中筛选宿主细胞免疫、自噬和氧化还原电位的效应物。他们从婴儿微生物组中确定的生物活性扩大了我们对微生物效应器的理解，这些微生物效应器已知调节宿主途径。
The human microbiota plays a critical role in host health. Proper development of the infant microbiome is particularly important. Its dysbiosis leads to both short-term health issues and long-term disorders lasting into adulthood. A central way in which the microbiome interacts with the host is through the production of effector molecules, such as proteins and small molecules. Here, a metagenomic library constructed from 14 infant stool microbiomes is analyzed for the production of effectors that modulate three distinct host pathways: immune response (nuclear factor κB [NF-κB] activation), autophagy (LC3-B puncta formation), and redox potential (NADH:NAD ratio). We identify microbiome-encoded bioactive metabolites, including commendamide and hydrogen sulfide and their associated biosynthetic genes, as well as a previously uncharacterized autophagy-inducing operon from Klebsiella spp. This work extends our understanding of microbial effector molecules that are known to influence host pathways. Parallel functional screening of metagenomic libraries can be easily expanded to investigate additional host processes. Construction of a metagenomic library from stool of infants A multiplexed screen for bacterial effectors of host cellular processes Identification of microbiome-encoded effectors hydrogen sulfide and commendamide The products of a Klebsiella pneumoniae operon induce autophagy Piscotta et al. screen a metagenomic library constructed from 14 infant stool microbiomes for effectors of host cell immunity, autophagy, and redox potential. The bioactivities they identify from the infant microbiome expand our understanding of microbial effectors that are known to modulate host pathways.
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影响因子：
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