Immunology Program, School of Medicine, Stanford University , Stanford, California, USA.
Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine, Stanford University , Stanford, California, USA.
mSystems. 2023 Aug 31;8(4):e0049723. doi: 10.1128/msystems.00497-23. Epub 2023 Aug 1.
Bacteriophages, viruses that parasitize bacteria, are known to be abundant at sites of bacterial colonization, but the relationship between phages and bacteria at sites of infection is unclear. Bacteriophages are highly specific to their bacterial host species, and so we hypothesize that phage populations would mirror those of bacterial pathogens within infected tissues. To test this, here we study publicly available cell-free DNA (cfDNA) generated using next-generation sequencing of infected bodily fluids, including urine, joint fluid, peritoneal fluid, bronchoalveolar lavage fluid, cerebrospinal fluid, and abscess fluid, as well as uninfected control samples. These were analyzed using a computational pipeline for identifying bacteriophage sequences in cfDNA. We find that bacteriophage sequences are present in both infected and uninfected bodily fluids and represent a variety of bacteriophage morphologies and bacterial hosts. Additionally, phages from , , and are overrepresented both in terms of proportion and diversity in fluids infected with these same pathogens. These data indicate that phages reflect the relative abundance of their bacterial hosts at sites of infection. Bacteriophage sequences may help inform future investigative and diagnostic approaches that utilize cell-free DNA to study the microbiome within infected tissues. IMPORTANCE Bacteriophages are an active area of investigation in microbiome research, but most studies have focused on phage populations at sites of bacterial colonization. Little is known about bacteriophage ecology at sites of active infection. To address this gap in knowledge, we utilized a publicly available data set to study bacteriophage populations in cell-free DNA collected from sites of infection. We find that phages reflect the relative abundance of their bacterial hosts at sites of infection. These studies may lead to future investigative and diagnostic approaches that incorporate phages as well as bacterial cell-free DNA.
噬菌体是寄生于细菌的病毒，已知在细菌定植的部位大量存在，但噬菌体与感染部位细菌之间的关系尚不清楚。噬菌体对其细菌宿主具有高度特异性，因此我们假设噬菌体种群将反映感染组织中细菌病原体的种群。为了验证这一点，我们在这里研究了从感染的体液（包括尿液、关节液、腹腔液、支气管肺泡灌洗液、脑脊液和脓肿液）以及未感染的对照样本中使用下一代测序生成的公开可用的无细胞 DNA (cfDNA)。我们使用一种计算管道来分析 cfDNA 中的噬菌体序列。我们发现噬菌体序列存在于感染和未感染的体液中，并代表各种噬菌体形态和细菌宿主。此外，来自 、 和 的噬菌体在这些相同病原体感染的体液中无论是在比例还是多样性方面都存在过表达。这些数据表明噬菌体反映了感染部位其细菌宿主的相对丰度。噬菌体序列可能有助于为未来利用无细胞 DNA 研究感染组织内微生物组的研究提供信息，并为调查和诊断方法提供依据。
重要性 噬菌体是微生物组研究中一个活跃的研究领域，但大多数研究都集中在细菌定植部位的噬菌体种群上。对于活跃感染部位的噬菌体生态学知之甚少。为了解决这一知识空白，我们利用公开可用的数据集研究了从感染部位收集的无细胞 DNA 中噬菌体种群。我们发现噬菌体反映了感染部位其细菌宿主的相对丰度。这些研究可能会导致未来的调查和诊断方法将噬菌体以及细菌无细胞 DNA 结合起来。
