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A Genomic Toolkit for the Mechanistic Dissection of Intractable Human Gut Bacteria.
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2020-04-28 , DOI: 10.1016/j.chom.2020.04.006
Jordan E Bisanz 1 , Paola Soto-Perez 1 , Cecilia Noecker 1 , Alexander A Aksenov 2 , Kathy N Lam 1 , Grace E Kenney 3 , Elizabeth N Bess 1 , Henry J Haiser 4 , Than S Kyaw 1 , Feiqiao B Yu 5 , Vayu M Rekdal 3 , Connie W Y Ha 6 , Suzanne Devkota 6 , Emily P Balskus 3 , Pieter C Dorrestein 2 , Emma Allen-Vercoe 7 , Peter J Turnbaugh 8
Affiliation  

Despite the remarkable microbial diversity found within humans, our ability to link genes to phenotypes is based upon a handful of model microorganisms. We report a comparative genomics platform for Eggerthella lenta and other Coriobacteriia, a neglected taxon broadly relevant to human health and disease. We uncover extensive genetic and metabolic diversity and validate a tool for mapping phenotypes to genes and sequence variants. We also present a tool for the quantification of strains from metagenomic sequencing data, enabling the identification of genes that predict bacterial fitness. Competitive growth is reproducible under laboratory conditions and attributable to intrinsic growth rates and resource utilization. Unique signatures of in vivo competition in gnotobiotic mice include an adhesin enriched in poor colonizers. Together, these computational and experimental resources represent a strong foundation for the continued mechanistic dissection of the Coriobacteriia and a template that can be applied to study other genetically intractable taxa.



中文翻译:

用于难治性人类肠道细菌机械解剖的基因组工具包。

尽管在人类体内发现了显着的微生物多样性,但我们将基因与表型联系起来的能力是基于少数模型微生物。我们报告了一个关于Eggerthella lenta和其他 Coriobacteriia的比较基因组学平台,这是一种与人类健康和疾病广泛相关的被忽视的分类群。我们发现了广泛的遗传和代谢多样性,并验证了一种将表型映射到基因和序列变体的工具。我们还提供了一种用于从宏基因组测序数据中量化菌株的工具,从而能够识别预测细菌适应性的基因。竞争性增长在实验室条件下是可复制的,可归因于内在增长率和资源利用率。体内的独特特征无菌小鼠中的竞争包括富含不良殖民者的粘附素。总之,这些计算和实验资源代表了继续对 Coriobacteriia 进行机械解剖的强大基础和可用于研究其他遗传难治性分类群的模板。

更新日期:2020-04-28
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