25 Interactions between cystic fibrosis (CF) and non-CF isolates of Aspergillus fumigatus and Pseudomonas aeruginosa in the development of a co-culture infection model for testing novel therapeutics

Abstract

Polymicrobial infections such as those with the fungus Aspergillus fumigatus and the bacterium Pseudomonas aeruginosa are frequently reported in CF but the clinical significance of A. fumigatus colonisation is uncertain. Whilst co-infections are common, co-localisation of bacteria and fungi within the lung is less well known. We are developing a polymicrobial infection model to examine these interactions in vitro to test therapeutics against this system. Objective We examined interactions between P. aeruginosa and A. fumigatus strains, from both CF and non-CF isolates to check for antagonism or tolerance and are developing a high throughput fluorescent screening technique to examine growth of either component. Methods Co-culture on solid agar to screen for antagonism. Time-of-kill experiments on selective growth media and fluorescent labelling of live A. fumigatus and P. aeruginosa co-cultures Results Initial screening further demonstrates the ability of non-CF P. aeruginosa strain PAO1 to inhibit the growth of A. fumigatus. All 6 CF-adapted strains tested, however, lacked this inhibitory activity. Initial results also show in vitro co-culture alters P. aeruginosa susceptibility to antibiotics by reducing time of kill by 1 h to tobramycin treatment regardless of CF background. Conclusion Whilst the presence of A. fumigatus in CF isn't considered life-threatening, as in immunocompromised patients, in vitro results suggest potential adaptations in P. aeruginosa CF strains toward co-existence with the host which make them less antagonistic toward A. fumigatus. We also demonstrate potential interactions that might impact antimicrobial therapy.