Consequences of Direct Viral-Bacterial Interactions

肺炎链球菌和流感在合并感染期间的协同作用长期以来一直被忽视。 认可.我们的数据表明，这种协同作用在物理层面上是有效的，因为我们提供了以下证据： 甲型流感病毒（IAV）与S.肺炎，提供健身的好处， 病原体我们有强有力的实验证据表明IAV直接与S.肺炎，促进 增强的细菌体外粘附和增强的体内定殖和传播。这种亲密 病毒和细菌表面之间的相互作用不限于S。肺炎，因为结合是 在人类呼吸道的多种细菌居民中观察到， 葡萄球菌属、莫拉菌属和嗜血杆菌属。IAV与细菌表面的关系是 互惠互利，因为与特定细菌物种结合的IAV表现出显着增强 环境稳定性，只有当与细菌复合时，IAV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-细菌合作期间的协同作用， 在侵入性疾病和传播过程中的感染。本提案的总体目标是， 对IAV-肺炎球菌直接结合如何发生以及这些结合的影响的机械理解 宿主与病原体之间的相互作用。我们假设IAV和 细菌是由两种病原体的特定因子介导的， 细菌和IAV影响呼吸道感染。呼吸道病原体之间的相互作用 可能被低估为呼吸道感染期间病毒-细菌协同作用的潜在机制。

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.