Elexacaftor/tezacaftor/ivacaftor (Trikafta(R)) does not affect the growth of Aspergillus fumigatus in vitro

Fungal infection, especially allergic bronchopulmonary aspergillosis, is a leading cause of infection-associated morbidity and death in patients with cystic fibrosis. We have previously discovered that the new leading therapeutic treatment in cystic fibrosis, CFTR modulators Elexakaftor/Tezacaftor/Ivacaftor (ETI, Trikafta(R)), drastically reduces the colonization and infection by Aspergillus fumigatus. However, the reasons for this decrease in patients are not known so far. In this study we have shown, using A. fumigatus reference strains and strains isolated from patients with cystic fibrosis, that CFTR modulators have no discernable impact on fungal growth in vitro. These results are consistent regardless of drugs concentration, demonstrating that treatment does not exert a direct antimicrobial or stimulatory effect in vitro on A. fumigatus conidia growth, when exposed to actual in vivo CFTR modulators concentration.