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. Video abstract.

中文翻译：

---

流感感染期间人类上呼吸道抗生素耐药性和宿主-微生物组相互作用的表征。

背景 人类呼吸道微生物组中抗生素抗性基因 (ARG) 的丰度和多样性仍然缺乏特征。在流感病毒感染的情况下，已知病毒、宿主和具有致病潜力的常驻细菌之间的相互作用会使疾病复杂化和恶化，导致合并感染并增加受感染个体的发病率和死亡率。当病原菌获得抗生素耐药性时，它们就更难治疗，也成为全球健康问题。上呼吸道 ARG 表达的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 37 人参加了尼加拉瓜马那瓜的家庭流感传播研究 (HITS)，被选中进行这项研究。我们对鼻腔和咽喉拭子样本进行了宏转录组学和 16S rRNA 基因测序分析，并对血液样本进行了宿主转录组分析。个体根据其微生物基因表达谱分为两组，其中几个微生物途径富含组间差异表达的基因。我们还分析了抗生素抗性基因表达，并确定大约 25% 的序列读数对应于映射到肺炎链球菌和金黄色葡萄球菌的抗生素抗性基因。在构建了 ARG 表达与宿主基因共表达的综合网络之后，我们确定了几种宿主关键调节因子，这些调节因子参与宿主对流感病毒和细菌感染的反应，和与特定抗生素抗性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中抗生素耐药性基因的表达。宿主对流感感染的全身反应与抗生素抗性基因表达之间的相互作用突出了病毒-细菌共感染在流感等急性呼吸道感染中的重要性。视频摘要。宿主对流感感染的全身反应与抗生素抗性基因表达之间的相互作用突出了病毒-细菌共感染在流感等急性呼吸道感染中的重要性。视频摘要。宿主对流感感染的全身反应与抗生素抗性基因表达之间的相互作用突出了病毒-细菌共感染在流感等急性呼吸道感染中的重要性。视频摘要。