[S6-2] Pathogenic streptococci exploit cell adhesion molecules for establishment of bacterial infection
Influenza A virus (IAV) infection predisposes the host to secondary bacterial pneumonia, a major cause of morbidity and mortality during influenza epidemics. However, the underlying viral-bacterial synergy mechanism leading to disease progression has remained elusive, thus hampering production of effective prophylactic and therapeutic intervention options. Recently, we focused on interactions of IAV-infected cells with pathogenic streptococci, such as Streptococcus pneumoniae and Streptococcus pyogenes, which revealed ectopic findings showing the endoplasmic reticulum chaperon GP96 on the surface of infected cells. Notably, efficient bacterial adherence to epithelial cells was gained by interactions with extracellular GP96 and integrin αV, with surface expression mediated by GP96 chaperone activity. Furthermore, adherence abrogation was gained by chemical inhibition or genetic knockout of GP96, as well as addition of RGD peptide. IAV infection also induced activation of calpains and Snail1, which are responsible for degradation and transcriptional repression of junctional proteins in the host, respectively, thus indicating increased bacterial translocation across the epithelial barrier. In this symposium, we will introduce our recent findings regarding the mechanism underlying this cell adhesion molecule-dependent viral-bacterial synergy related to disease progression.