Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, 10003, USA.
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Microbiome. 2020 Mar 17;8(1):39. doi: 10.1186/s40168-020-00803-2.
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.
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.
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.
人类呼吸道微生物组中抗生素耐药基因（ARGs）的丰度和多样性仍未得到充分描述。在流感病毒感染的情况下，病毒、宿主和具有潜在致病性的常驻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，并增加感染个体的发病率和死亡率。当致病性细菌获得抗生素耐药性时，它们更难治疗，这是全球健康关注的问题。对上呼吸道中 ARG 表达的特征描述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。
从尼加拉瓜马那瓜的家庭流感传播研究（HITS）中选择了 37 名参与者进行本研究。我们对鼻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。根据他们的微生物基因表达谱，个体聚类为两组，有几个微生物途径富集了两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%与抗生素耐药基因相对应的序列读数映射到肺炎链球菌和金黄色葡萄球菌。在构建 ARG 表达与宿主基因共表达的综合网络后，我们确定了几个宿主关键调节剂，这些调节剂参与宿主对流感病毒和细菌感染的反应，以及与特定抗生素耐药基因相关的宿主基因途径。
这项研究表明，宿主对流感感染的反应可以通过影响微生物群落结构和整体微生物基因表达，间接影响呼吸道中的抗生素耐药基因表达。宿主对流感感染的系统反应与抗生素耐药基因表达之间的相互作用突出了急性呼吸道感染（如流感）中病毒-细菌合并感染的重要性。视频摘要。
