Metrics of Antifungal Effects of Ciprofloxacin on Aspergillus fumigatus Planktonic Growth and Biofilm Metabolism; Effects of Iron and Siderophores

Abstract

Pseudomonas aeruginosa and Aspergillus fumigatus 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 Pseudomonas aeruginosa. CIP binds iron, and it is unclear what effect this complex would have on the mycobiome. The effects of CIP on Aspergillus were dependent on the iron levels present, and on the presence of Aspergillus 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 Aspergillus metabolism, presumably owing to iron chelation. CIP interfered with the metabolism and growth of an Aspergillus 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 Pseudomonas–Aspergillus co-infections may increase the fungal burden.

Development of Gallium(III) as an Antimicrobial Drug Targeting Pathophysiologic Iron Metabolism of Human Pathogens

“…Aspergillus fumigatus and Fusarim oxysporum also possess siderophore-like effectors that can take up certain iron chelators, including the iron chelated to the antibiotic ciprofloxacin, which can greatly enhance biofilm formation and growth. ,, …”

“…cir1 is so important to pathogenic C. neoformans that knock out mutants became non-pathogenic 57 Aspergillus fumigatus and Fusarim oxysporum also possess siderophore-like effectors that can take up certain iron chelators, including the iron chelated to the antibiotic ciprofloxacin, which can greatly enhance biofilm formation and growth. 21,59,60 The increased availability of free iron that occurs at low pH has also been postulated to contribute to the pathogenesis of infections with Mucorales sp. in patients with poorly controlled diabetes.…”