Consequences of Direct Viral-Bacterial Interactions

病毒-细菌直接相互作用的后果

• 批准号: 10437204
• 负责人: Juan Cesar Federico Ortiz-Marquez
• 金额: $ 53.11万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-20 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10437204
• 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; 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.

肺炎链球菌和流感在合并感染过程中的协同作用长期以来一直是 被认可了。我们的数据表明，这种协同作用在物理层面上是有效的，因为我们提供了证据 与肺炎链球菌表面结合的甲型流感病毒(IAV)，对两人都有好处 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，从而促进 增强细菌在体外的黏附，增强体内的定植和扩散。这份亲密 病毒与细菌表面的相互作用并不局限于肺炎链球菌，正如结合一样。 观察人类呼吸道的多种细菌栖息地，包括多种 葡萄球菌、莫拉氏菌和嗜血杆菌。IAV和细菌表面的关系是 互惠互利，因为与特定细菌物种结合的IAV显著增强 环境稳定，IAV只有在与细菌复合时才能在干燥过程中保持感染性。 我们的长期目标是更好地了解IAV-细菌协同作用过程中的协同作用 侵袭性疾病和传播过程中的感染。这项建议的总体目标是获得 对IAV-肺炎球菌直接结合如何发生以及它们的影响的机械理解 寄主-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，它们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 作为呼吸道感染期间病毒-细菌协同作用的潜在机制，可能被低估。