Metrics of Antifungal Effects of Ciprofloxacin on <i>Aspergillus fumigatus</i> Planktonic Growth and Biofilm Metabolism; Effects of Iron and Siderophores
2022
Gabriele Sass | Lynn Scherpe | Marife Martinez | Julianne J. Marsh | David A. Stevens
<i>Pseudomonas aeruginosa</i> and <i>Aspergillus fumigatus</i> frequently coexist in the airways of immunocompromised patients or individuals with cystic fibrosis. Ciprofloxacin (CIP) is a synthetic quinolone antibiotic commonly used to treat bacterial infections, such as those produced by <i>Pseudomonas aeruginosa.</i> CIP binds iron, and it is unclear what effect this complex would have on the mycobiome. The effects of CIP on <i>Aspergillus</i> were dependent on the iron levels present, and on the presence of <i>Aspergillus</i> siderophores. We found that CIP alone stimulated wildtype planktonic growth, but not biofilm metabolism. At high concentrations, CIP antagonized a profungal effect of iron on wildtype <i>Aspergillus</i> metabolism, presumably owing to iron chelation. CIP interfered with the metabolism and growth of an <i>Aspergillus</i> siderophore mutant, with the effect on metabolism being antagonized by iron. CIP acted synergistically with iron on the growth of the mutant, and, to a lesser extent, the wildtype. In summary, CIP can increase fungal growth or affect fungal metabolism, depending on the local iron concentration and available siderophores. Therefore, high local CIP concentrations during treatment of <i>Pseudomonas–Aspergillus</i> co-infections may increase the fungal burden.
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