The cystic fibrosis treatment Trikafta affects the growth, viability, and cell wall of <i>Aspergillus fumigatus</i> biofilms

Abstract

PwCF commonly test positive for pathogenic fungi, and more than 90% of the cystic fibrosis patient population is approved for the modulator treatment, Trikafta. Therefore, it is critical to understand how fungal communities, specifically <i>A. fumigatus</i>, respond to Trikafta exposure. Therefore, we sought to determine whether Trikafta impacted the biology of <i>A. fumigatus</i> biofilms. Our data demonstrate that Trikafta reduces biomass in several laboratory strains as well as clinical strains isolated from the expectorated sputum of pwCF. Furthermore, Trikafta reduces fungal viability and the capacity of biofilms to recover following treatment. Of particular importance, Trikafta affects how <i>A. fumigatus</i> biofilms respond to cell wall stressors, suggesting that Trikafta modulates components of the cell wall. Since the cell wall directly affects how a host immune system will respond to and effectively neutralize pathogens, our work, demonstrating that Trikafta impacts the <i>A. fumigatus</i> cell wall, is potentially highly relevant to fungal-induced disease pathogenesis.