Elucidating the augmented resistance profile of Scedosporium/Lomentospora species to azoles in a cystic fibrosis mimic environment.

This article focuses on the increased azole antifungal resistance of Scedosporium and Lomentospora species—filamentous fungi frequently isolated from cystic fibrosis (CF) patients—when grown in a synthetic CF sputum medium (SCFM) compared to the standard RPMI-1640 medium. The study found that minimum inhibitory concentrations (MICs) for six azoles, including voriconazole and fluconazole, were significantly higher in SCFM, indicating enhanced tolerance. Investigations revealed that while efflux pump activity contributes partially to azole resistance, SCFM-grown cells exhibit decreased sterol content and altered sterol profiles, leading to increased membrane fluidity and adaptive cellular changes that support survival under azole stress. These findings highlight the complex mechanisms underlying antifungal resistance in CF-like environments and underscore challenges in treating scedosporiosis in CF patients.