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Bioorthogonal non-canonical amino acid tagging reveals translationally active subpopulations of the cystic fibrosis lung microbiota.

生物正交非经典氨基酸标记揭示囊性纤维化肺微生物群的翻译活性亚群。

  • 影响因子:12.19
  • DOI:10.1038/s41467-020-16163-2
  • 作者列表:"Valentini TD","Lucas SK","Binder KA","Cameron LC","Motl JA","Dunitz JM","Hunter RC
  • 发表时间:2020-05-08
Abstract

:Culture-independent studies of cystic fibrosis lung microbiota have provided few mechanistic insights into the polymicrobial basis of disease. Deciphering the specific contributions of individual taxa to CF pathogenesis requires comprehensive understanding of their ecophysiology at the site of infection. We hypothesize that only a subset of CF microbiota are translationally active and that these activities vary between subjects. Here, we apply bioorthogonal non-canonical amino acid tagging (BONCAT) to visualize and quantify bacterial translational activity in expectorated sputum. We report that the percentage of BONCAT-labeled (i.e. active) bacterial cells varies substantially between subjects (6-56%). We use fluorescence-activated cell sorting (FACS) and genomic sequencing to assign taxonomy to BONCAT-labeled cells. While many abundant taxa are indeed active, most bacterial species detected by conventional molecular profiling show a mixed population of both BONCAT-labeled and unlabeled cells, suggesting heterogeneous growth rates in sputum. Differentiating translationally active subpopulations adds to our evolving understanding of CF lung disease and may help guide antibiotic therapies targeting bacteria most likely to be susceptible.

摘要

: 囊性纤维化肺部微生物群的独立培养研究对疾病的多微生物基础提供了很少的机制见解。破译个体分类群对CF发病机制的具体贡献需要全面了解其在感染部位的生态生理学。我们假设只有CF微生物群的一个子集是翻译活性的,并且这些活性在受试者之间不同。在这里,我们应用生物正交非经典氨基酸标签 (BONCAT) 来可视化和定量咳痰中的细菌翻译活性。我们报告了BONCAT标记的百分比 (即活性) 细菌细胞在受试者之间显著不同 (6-56%)。我们使用荧光激活细胞分选 (FACS) 和基因组测序将分类学分配给BONCAT标记的细胞。虽然许多丰富的分类群确实是有活性的,但通过常规分子谱检测到的大多数细菌种类显示出BONCAT标记和未标记细胞的混合群体,表明痰中的生长速率不均匀。区分翻译活性亚群增加了我们对CF肺病不断发展的理解,并可能有助于指导针对最可能易感细菌的抗生素疗法。

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影响因子:4.91
发表时间:2020-03-01
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DOI:10.1097/SLA.0000000000003022
作者列表:["Pea A","Yu J","Marchionni L","Noe M","Luchini C","Pulvirenti A","de Wilde RF","Brosens LA","Rezaee N","Javed A","Chianchiano P","Gobbo S","Regi P","Salvia R","Bassi C","He J","Weiss MJ","Cameron JL","Offerhaus GJA","Hruban RH","Lawlor RT","Scarpa A","Heaphy CM","Wood LD","Wolfgang CL"]

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影响因子:0.50
发表时间:2020-02-01
DOI:10.1080/00015458.2018.1538283
作者列表:["Aksel B","Güven HE"]

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影响因子:1.74
发表时间:2020-01-01
DOI:10.1016/j.jfma.2019.01.015
作者列表:["Yang SH","Guo JC","Hsu C","Kuo SH","Tien YW","Cheng AL","Yeh KH"]

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