Brilacidin, a host defense peptide mimetic, potentiates ibrexafungerp antifungal activity against the human pathogenic fungus Aspergillus fumigatus

Thaila Fernanda Dos Reis; Camila Diehl; Camila Figueiredo Pinzan; Patrícia Alves de Castro; Gustavo H Goldman

doi:10.1101/2024.04.05.588305

Brilacidin, a host defense peptide mimetic, potentiates ibrexafungerp antifungal activity against the human pathogenic fungus Aspergillus fumigatus

bioRxiv [Preprint]. 2024 Apr 5:2024.04.05.588305. doi: 10.1101/2024.04.05.588305.

Authors

Thaila Fernanda Dos Reis¹, Camila Diehl¹, Camila Figueiredo Pinzan¹, Patrícia Alves de Castro¹, Gustavo H Goldman^{1

2}

Affiliations

¹ Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
² National Institute of Science and Technology in Human Pathogenic Fungi, Brazil.

Abstract

Aspergillus fumigatus is the primary etiological agent of aspergillosis. Here, we show that the host defense peptide mimetic, brilacidin (BRI) can potentiate ibrexafungerp (IBX) against clinical isolates of A. fumigatus. CAS-resistant strains with mutations in fks1 that encodes the 1,3-β-D-glucan synthase are not IBX-resistant and BRI+IBX can inhibit their growth. The combination of BRI+IBX plays a fungicidal role, increases the fungal cell permeability and decreases the fungal survival in the presence of A549 epithelial cells.

Keywords: Aspergillus fumigatus; brilacidin; drug resistance; ibrexafungerp.

Publication types

Preprint

Grants and funding

R01 AI153356/AI/NIAID NIH HHS/United States