Strain-Resolved Dynamics of the Lung Microbiome in Patients with Cystic Fibrosis.
Strain-Resolved Dynamics of the Lung Microbiome in Patients with Cystic Fibrosis.
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DOI：
10.1128/mbio.02863-20
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发表时间：
2021-03-09
期刊：
影响因子：
6.4
通讯作者：
von Mering C
中科院分区：
文献类型：
--
作者：
Dmitrijeva M;Kahlert CR;Feigelman R;Kleiner RL;Nolte O;Albrich WC;Baty F;von Mering C
囊性纤维化患者经常遭受由定植的致病菌和共生菌引起的反复呼吸道感染。尽管现代疗法有时可以通过改善导致疾病的蛋白质的残余功能来缓解呼吸道症状，但慢性呼吸道感染的治疗仍然是一个问题。在囊性纤维化中，动态且复杂的微生物病原体和共生菌群落可以在肺部定植。从肺痰中培养的分离株揭示了病原体菌株、序列变异和表型的高度变异性；疾病进展可能取决于感染谱系的精确组合。然而，常规临床方案对殖民者群体的概述有限。因此，对感染谱系进行更全面、更精确的识别和表征可以有助于做出相应的治疗决策。在这里，我们描述了对 4 名囊性纤维化患者的纵向跟踪，这些患者表现出极端的临床表型，因此是从 11 名患者的试点队列中选出的，并重复采样了一年多。对肺痰进行宏基因组测序后，我们发现可以轻松建立个体殖民者谱系的分类学身份。至关重要的是，即使是表面克隆的病原体也可以在序列水平上细分为多个亚系。通过跟踪随时间变化的个体等位基因差异，无组装聚类方法使我们能够重建具有明显结构差异的多个谱系特异性基因组。我们的研究展示了一种独立于培养物的鸟枪法宏基因组学方法，用于纵向追踪亚谱系病原体动态，开辟了使用此类方法通过提供囊性纤维化肺微生物组的高分辨率常规特征来协助监测疾病进展的可能性。
Cystic fibrosis patients frequently suffer from recurring respiratory infections caused by colonizing pathogenic and commensal bacteria. Although modern therapies can sometimes alleviate respiratory symptoms by ameliorating residual function of the protein responsible for the disorder, management of chronic respiratory infections remains an issue. In cystic fibrosis, dynamic and complex communities of microbial pathogens and commensals can colonize the lung. Cultured isolates from lung sputum reveal high inter- and intraindividual variability in pathogen strains, sequence variants, and phenotypes; disease progression likely depends on the precise combination of infecting lineages. Routine clinical protocols, however, provide a limited overview of the colonizer populations. Therefore, a more comprehensive and precise identification and characterization of infecting lineages could assist in making corresponding decisions on treatment. Here, we describe longitudinal tracking for four cystic fibrosis patients who exhibited extreme clinical phenotypes and, thus, were selected from a pilot cohort of 11 patients with repeated sampling for more than a year. Following metagenomics sequencing of lung sputum, we find that the taxonomic identity of individual colonizer lineages can be easily established. Crucially, even superficially clonal pathogens can be subdivided into multiple sublineages at the sequence level. By tracking individual allelic differences over time, an assembly-free clustering approach allows us to reconstruct multiple lineage-specific genomes with clear structural differences. Our study showcases a culture-independent shotgun metagenomics approach for longitudinal tracking of sublineage pathogen dynamics, opening up the possibility of using such methods to assist in monitoring disease progression through providing high-resolution routine characterization of the cystic fibrosis lung microbiome.