Consequences of Direct Viral-Bacterial Interactions

病毒-细菌直接相互作用的后果

• 批准号: 10420634
• 负责人: Jason W. Rosch
• 金额: $ 52.28万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-05 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10420634
• 关键词: Adherence; Area; Bacteria; Bacterial Adhesion; Bacterial Pneumonia; Bacteriophages; Binding; Characteristics; Complex; Coupled; Data; Desiccation; Disease; Epithelial Cells; Flow Cytometry; Future; Genes; Genus staphylococcus; Goals; Hemagglutinin; Hemophilus; Human; Immune response; In Vitro; Infection; Influenza; Influenza A virus; Intervention; Investigation; Mediating; Modeling; Moraxella; Mus; Neuraminidase; Polysaccharides; Population; Predisposition; Proteins; Respiratory System; Respiratory Tract Infections; Role; Secondary to; Streptococcus pneumoniae; Surface; Viral; Viral Hemagglutinins; Virulence; Virus; Virus Diseases; bacterial genetics; base; co-infection; cross immunity; disease transmission; experimental study; fitness; glycosylation; human disease; in vivo; insight; mutant; novel; pathogen; respiratory; respiratory pathogen; respiratory virus; synergism; therapeutic development; tissue tropism; transcriptome sequencing; transmission process; transposon sequencing; viral transmission

The synergy between Streptococcus pneumoniae and influenza during co-infection has long been recognized. Our data indicate that this synergy is operative on a physical level, as we provide evidence of influenza A virus (IAV) binding to the surface of S. pneumoniae, providing fitness benefits to both pathogens. We have strong experimental evidence that IAV directly binds to S. pneumoniae, facilitating enhanced bacterial adhesion in vitro and enhanced colonization and dissemination in vivo. This intimate interaction between virus and the bacterial surface is not limited to S. pneumoniae, as binding was observed with multiple bacterial inhabitants of the human respiratory tract including species of Staphylococcus, Moraxella, and Haemophilus. The relationship between IAV and the bacterial surface is mutually beneficial, as IAV bound to specific bacterial species demonstrate dramatically enhanced environmental stability, with IAV retaining infectivity during desiccation only when in complex with bacteria. Our long-term goal is to gain a greater understanding of the synergies operative during IAV-bacterial co- infections during both invasive disease and transmission. The overall objective of this proposal is to gain a mechanistic understanding of how direct IAV-pneumococcal binding occurs and the impact of these interactions on host-pathogen interactions. We hypothesize that the direct interactions between IAV and bacteria are mediated by specific factors of both pathogens and that the direct interactions between bacteria and IAV impact respiratory infection. The interkingdom interplay between respiratory pathogens may be underappreciated as a mechanism underlying viral–bacterial synergy during respiratory infection.

肺炎链球菌与流感在共同感染期间的协同作用长期以来一直被认为 认可。我们的数据表明，这种协同作用在物理层面上发挥作用，因为我们提供了以下证据： 甲型流感病毒 (IAV) 与肺炎链球菌表面结合，为两者提供健康益处 病原体。我们有强有力的实验证据表明 IAV 直接与肺炎链球菌结合，促进 增强细菌体外粘附，增强体内定植和传播。这种亲密的 病毒和细菌表面之间的相互作用并不限于肺炎链球菌，因为结合是 观察到人类呼吸道的多种细菌居民，包括以下物种 葡萄球菌、莫拉氏菌和嗜血杆菌。 IAV与细菌表面的关系为 互惠互利，因为 IAV 与特定细菌物种的结合表现出显着增强 环境稳定性，IAV 仅在与细菌复合时才在干燥过程中保留感染性。 我们的长期目标是更好地了解 IAV-细菌协同作用期间的协同作用 侵袭性疾病和传播过程中的感染。该提案的总体目标是获得 了解 IAV-肺炎球菌直接结合如何发生及其影响的机制 宿主-病原体相互作用的相互作用。我们假设 IAV 和 IAV 之间的直接相互作用 细菌是由两种病原体的特定因素介导的，并且两者之间的直接相互作用 细菌和 IAV 影响呼吸道感染。呼吸道病原体之间的跨界相互作用 作为呼吸道感染过程中病毒-细菌协同作用的潜在机制，它可能被低估。