Aspergillus fumigatus coinfection facilitates Pseudomonas aeruginosa chronicity within an ex-vivo pig lung model.

Pseudomonas aeruginosa and Aspergillus fumigatus represent the dominant bacterial and fungal pathogens in the lungs of adults with cystic fibrosis. Understanding how these species interact with each other and the host may provide insight into pathology and microbial succession in the lung. The ex vivo pig lung model is suitable for studying host responses to pathogens in an ethical and cost-effective manner due to its rich cell complexity and anatomical and immunological similarities to humans. Metagenomic analysis demonstrated that A. fumigatus promoted the proliferation of Pseudomonadota and P. aeruginosa in coinfected explants. Proteomic analysis of coinfected alveolar lung explants identified reduced virulence of A. fumigatus in competition with P. aeruginosa with reductions in abundance of dipeptidyl-peptidase 5 (-10.30-fold) and thioredoxin reductase gliT (-11.72-fold) and a reduction in amide biosynthetic processes. P. aeruginosa flourished in coinfected tissue and increased protein translation and amino acid biosynthesis and cellular nitrogen utilization. Examination of changes in the porcine proteome indicated specific nutritional utilization with A. fumigatus inducing greater complement activation and utilization of amino acids, while P. aeruginosa infection induced greater natural killer cell toxicity and potential butanoate metabolism from the host. Increased abundance of proteins associated with inflammation and immune activation was observed in coinfected samples relative to the mono-infected tissues. Coinfection also resulted in the reduction in abundance of ferritin and lactotransferrin, which may indicate elevated bioavailability of iron that could facilitate P. aeruginosa virulence.