<i>Fusobacterium nucleatum</i>Interaction with<i>Pseudomonas aeruginosa</i>Induces Biofilm-Associated Antibiotic Tolerance via<i>Fusobacterium</i>Adhesin A

Abstract

Respiratory infections with <i>Pseudomonas aeruginosa</i> or <i>Fusobacterium nucleatum</i> 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 <i>F. nucleatum</i> frequently coexisted with <i>P. aeruginosa</i> in the respiratory tract, and the number of <i>F. nucleatum</i> was negatively correlated with the lung function of AECOPD patients. The coculture of <i>P. aeruginosa</i> and <i>F. nucleatum</i> promoted bacterial proliferation and induced antibiotic tolerance through the formation of a dense biofilm surrounded by excessive Pel and Psl polysaccharides. Moreover, <i>Fusobacterium</i> adhesin A (FadA), rather than <i>F. nucleatum</i> spent medium, induced antibiotic tolerance of the <i>P. aeruginosa</i> biofilm. These results indicate that <i>F. nucleatum</i> is a biomarker of lung function decline in AECOPD patients and interacts with <i>P. aeruginosa</i> in vitro to resist antibiotics via FadA, which would be a potential anti-infective target of these dual-species infection.