Respiratory virus co‐infection enhances Pseudomonas aeruginosa biofilm growth on airway epithelial cells (869.1)

Abstract

Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic resistant biofilm communities promotes airway colonization and accounts for disease progression in chronic lung disease patients. We hypothesized that respiratory viral co‐infection promotes P. aeruginosa biofilm growth and colonization. In the presence of respiratory syncytial virus (RSV) co‐infection, we observed a significant increase in P. aeruginosa biofilm formation on airway epithelial cells (AECs). RSV infection induces a potent antiviral innate immune response in AECs through interferon (IFN)‐λ signaling. IFN‐λ signaling is capable of recapitulating the RSV‐induced bacterial biofilm formation. We have isolated the biofilm stimulatory activity to purified exosomes in conditioned media obtained from AECs infected with RSV. Iron is essential to P. aeruginosa growth and biofilm maturation, and chelation of iron inhibits biofilm growth on human AECs. We observed increased levels of iron in conditioned media from RSV‐infected AECs and chelation of iron in the conditioned media blocked biofilm stimulation. RSV infection did not alter iron transporter abundance in the plasma membrane, but dramatically enhanced the epithelial transcytosis and apical secretion of exosome‐associated, iron‐bound transferrin. This represents the first study that links viral co‐infection, and the resulting iron transport defect, to the development of biofilms and chronic bacterial infections.Grant Funding Source: Supported by R00HL098342 and P30DK072506 (JMB)