Phage diversity in cell-free DNA identifies bacterial pathogens in human sepsis cases
Phage diversity in cell-free DNA identifies bacterial pathogens in human sepsis cases
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DOI：
10.1038/s41564-023-01406-x
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发表时间：
2023-06-12
影响因子：
28.3
通讯作者：
Bollyky, Paul L.
中科院分区：
文献类型：
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作者：
Haddock, Naomi L.;Barkal, Layla J.;Bollyky, Paul L.
噬菌体是一种感染细菌的病毒，在菌株和物种水平上对其细菌宿主具有很强的特异性。然而，噬菌体与相关细菌种群动态之间的关系尚不清楚。在这里，我们生成了一个计算管道来识别与血浆样本中无细胞DNA中的噬菌体及其细菌宿主相关的序列。对两个独立队列的分析，包括61名脓毒症患者和10名对照组的Stanford队列和224名脓毒症患者和167名对照组的SeqStudy队列，揭示了所有样本个体血浆中的循环吞噬体。此外，感染与病原体特异性噬菌体的过度代表有关，从而可以识别细菌病原体。我们发现有关噬菌体多样性的信息能够鉴定产生这些噬菌体的细菌，包括大肠杆菌的致病菌株。噬菌体序列同样可以用来区分密切相关的细菌种类，如金黄色葡萄球菌，一种常见的病原体，和凝固酶阴性葡萄球菌，一种常见的污染物。无噬菌体DNA在研究细菌感染方面可能具有实用价值。人血浆中无细胞DNA的噬菌体多样性可以帮助确定败血症期间致病性大肠杆菌和金黄色葡萄球菌。
Bacteriophages, viruses that infect bacteria, have great specificity for their bacterial hosts at the strain and species level. However, the relationship between the phageome and associated bacterial population dynamics is unclear. Here we generated a computational pipeline to identify sequences associated with bacteriophages and their bacterial hosts in cell-free DNA from plasma samples. Analysis of two independent cohorts, including a Stanford Cohort of 61 septic patients and 10 controls and the SeqStudy cohort of 224 septic patients and 167 controls, reveals a circulating phageome in the plasma of all sampled individuals. Moreover, infection is associated with overrepresentation of pathogen-specific phages, allowing for identification of bacterial pathogens. We find that information on phage diversity enables identification of the bacteria that produced these phages, including pathovariant strains of Escherichia coli. Phage sequences can likewise be used to distinguish between closely related bacterial species such as Staphylococcus aureus, a frequent pathogen, and coagulase-negative Staphylococcus, a frequent contaminant. Phage cell-free DNA may have utility in studying bacterial infections.Bacteriophage diversity in cell-free DNA within human plasma can help to specify pathogenic Escherichia coli and Staphylococcus aureus during sepsis.