AUTHOR=Sass Gabriele , Marsh Julianne J. , Shrestha Pallabi , Sabino Raquel , Stevens David A. 

TITLE=Synergy Between Pseudomonas aeruginosa Filtrates And Voriconazole Against Aspergillus fumigatus Biofilm Is Less for Mucoid Isolates From Persons With Cystic Fibrosis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.817315

DOI=10.3389/fcimb.2022.817315

ISSN=2235-2988

ABSTRACT=<p>Persons with cystic fibrosis (CF) frequently suffer from <italic>Pseudomonas aeruginosa</italic> and <italic>Aspergillus fumigatus</italic> co-infections. There is evidence that co-infections with these interacting pathogens cause airway inflammation and aggravate deterioration of lung function. We recently showed that <italic>P. aeruginosa</italic> laboratory isolates synergistically interact with the anti-fungal azole voriconazole (VCZ), inhibiting biofilm metabolism of several <italic>A. fumigatus</italic> laboratory strains. Interaction was usually mediated <italic>via</italic> pyoverdine, but also <italic>via</italic> pyocyanin or pyochelin. Here we used planktonic filtrates of 7 mucoid and 9 non-mucoid <italic>P. aeruginosa</italic> isolates from CF patients, as well as 8 isolates without CF origin, and found that all of these isolates interacted with VCZ synergistically at their IC50 as well as higher dilutions. CF mucoid isolates showed the weakest interactive effects. Four non-mucoid <italic>P. aeruginosa</italic> CF isolates produced no or very low levels of pyoverdine and did not reach an IC50 against forming <italic>A. fumigatus</italic> biofilm; interaction with VCZ still was synergistic. A VCZ-resistant <italic>A. fumigatus</italic> strain showed the same level of susceptibility for <italic>P. aeruginosa</italic> anti-fungal activity as a VCZ-susceptible reference strain. Filtrates of most <italic>Pseudomonas</italic> isolates were able to increase anti-fungal activity of VCZ on a susceptible <italic>A. fumigatus</italic> strain. This was also possible for the VCZ-resistant strain. In summary these data show that clinical <italic>P. aeruginosa</italic> isolates, at varying degrees, synergistically interact with VCZ, and that pyoverdine is not the only molecule responsible. These data also strengthen the idea that during co-infections of <italic>A. fumigatus</italic> and <italic>P. aeruginosa</italic> lower concentrations of VCZ might be sufficient to control fungal growth.</p>