Respiratory syncytial virus infection enhancesPseudomonas aeruginosabiofilm growth through dysregulation of nutritional immunity

Abstract

Clinical observations link respiratory virus infection andPseudomonas aeruginosacolonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development ofP.aeruginosainto highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients’ acquisition of chronicP.aeruginosainfections and respiratory virus infection, little is known about the mechanism by which chronicP.aeruginosainfections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondaryP.aeruginosabiofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotesP.aeruginosabiofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.