Fusobacterium nucleatum Interaction with Pseudomonas aeruginosa Induces Biofilm-Associated Antibiotic Tolerance via Fusobacterium Adhesin A

Respiratory infections with Pseudomonas aeruginosa or Fusobacterium nucleatum are associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and failure in antibiotic treatment. However, the impact of these dual-species interactions on the severity of chronic obstructive pulmonary disease (COPD) and biofilm antibiotic susceptibility remains poorly understood. This study demonstrated that F. nucleatum frequently coexisted with P. aeruginosa in the respiratory tract, and the number of F. nucleatum was negatively correlated with the lung function of AECOPD patients. The coculture of P. aeruginosa and F. nucleatum promoted bacterial proliferation and induced antibiotic tolerance through the formation of a dense biofilm surrounded by excessive Pel and Psl polysaccharides. Moreover, Fusobacterium adhesin A (FadA), rather than F. nucleatum spent medium, induced antibiotic tolerance of the P. aeruginosa biofilm. These results indicate that F. nucleatum is a biomarker of lung function decline in AECOPD patients and interacts with P. aeruginosa in vitro to resist antibiotics via FadA, which would be a potential anti-infective target of these dual-species infection.