Characterization of antibiotic resistance and host-microbiome interactions in the human upper respiratory tract during influenza infection
Characterization of antibiotic resistance and host-microbiome interactions in the human upper respiratory tract during influenza infection
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DOI：
10.1186/s40168-020-00803-2
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发表时间：
2020-03-17
期刊：
影响因子：
15.5
通讯作者：
Ghedin, Elodie
中科院分区：
文献类型：
--
作者：
Zhang, Lingdi;Forst, Christian, V;Ghedin, Elodie
背景：人类呼吸道微生物群中抗生素耐药基因(ARGs)的丰富性和多样性仍未得到很好的描述。在流感病毒感染的背景下，病毒、宿主和具有致病潜力的驻留细菌之间的相互作用已知会使疾病复杂化和恶化，导致合并感染，并增加感染者的发病率和死亡率。当病原菌获得抗生素耐药性时，它们更难治疗，并引起全球健康问题。ARG在上呼吸道的表达特征有助于更好地了解抗生素耐药性在流感相关细菌继发感染发病机制中的作用。结果：在尼加拉瓜马那瓜参加家庭流感传播研究(HITS)的37人进入本研究。我们对鼻咽拭子样本进行了变转录组学和16S rRNA基因测序分析，并对血液样本进行了宿主转录组谱分析。个体根据他们的微生物基因表达谱分成两组，几个微生物途径丰富了不同组之间差异表达的基因。我们还分析了抗生素耐药基因的表达，并确定大约25%的序列与定位于肺炎链球菌和金黄色葡萄球菌的抗生素耐药基因相对应。在构建ARG表达与宿主基因共表达的整合网络后，我们确定了参与宿主对流感病毒和细菌感染反应的几个关键调控因子，以及与特定抗生素耐药基因相关的宿主基因途径。结论：本研究表明，宿主对流感感染的反应可能通过影响微生物群落结构和整体微生物基因表达来间接影响呼吸道耐药基因的表达。宿主对流感感染的系统反应和抗生素耐药基因表达之间的相互作用突显了病毒-细菌联合感染在流感等急性呼吸道感染中的重要性。
Background: The abundance and diversity of antibiotic resistance genes (ARGs) in the human respiratory microbiome remain poorly characterized. In the context of influenza virus infection, interactions between the virus, the host, and resident bacteria with pathogenic potential are known to complicate and worsen disease, resulting in coinfection and increased morbidity and mortality of infected individuals. When pathogenic bacteria acquire antibiotic resistance, they are more difficult to treat and of global health concern. Characterization of ARG expression in the upper respiratory tract could help better understand the role antibiotic resistance plays in the pathogenesis of influenza-associated bacterial secondary infection.Results: Thirty-seven individuals participating in the Household Influenza Transmission Study (HITS) in Managua, Nicaragua, were selected for this study. We performed metatranscriptomics and 16S rRNA gene sequencing analyses on nasal and throat swab samples, and host transcriptome profiling on blood samples. Individuals clustered into two groups based on their microbial gene expression profiles, with several microbial pathways enriched with genes differentially expressed between groups. We also analyzed antibiotic resistance gene expression and determined that approximately 25% of the sequence reads that corresponded to antibiotic resistance genes mapped to Streptococcus pneumoniae and Staphylococcus aureus. Following construction of an integrated network of ARG expression with host gene co-expression, we identified several host key regulators involved in the host response to influenza virus and bacterial infections, and host gene pathways associated with specific antibiotic resistance genes.Conclusions: This study indicates the host response to influenza infection could indirectly affect antibiotic resistance gene expression in the respiratory tract by impacting the microbial community structure and overall microbial gene expression. Interactions between the host systemic responses to influenza infection and antibiotic resistance gene expression highlight the importance of viral-bacterial co-infection in acute respiratory infections like influenza.