Staphylococcus aureus enhances influenza A virus replication through modulation of host cell vesicular transport

Abstract

Influenza A virus (IAV) is a major respiratory pathogen that causes substantial morbidity and mortality worldwide. A significant complication of primary IAV infection is secondary bacterial co-infection. Here, we report that Staphylococcus aureus enhances IAV replication through the activity of the surface protein fibronectin-binding protein A (FnbA). The pro-viral activity of FnbA is conserved across multiple IAV strains and is associated with reduced abundance of the host vesicular trafficking proteins VPS26A and VTA1. FnbA does not substantially increase viral protein abundance or alter intracellular distribution. Instead, pro-viral activity is associated with a greater proportion of infectious progeny particles and increased release of infectious virions from infected cells. Thus, we identify FnbA as a bacterial factor that enhances IAV replication and demonstrate that S. aureus can manipulate host cell processes to promote the production and release of infectious virus.