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Brilacidin, a novel antifungal agent against Cryptococcus neoformans

Camila Diehl1, Camila Figueiredo Pinzan1, Patrícia Alves de Castro1

  • 1Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.

Mbio
|June 25, 2024
PubMed

Insights

Brilacidin (BRI) shows promise as a novel antifungal drug against Cryptococcus neoformans, effectively reducing fungal survival and lung infection. It also potentiates existing antifungal drugs like caspofungin (CAS).

Area of Science:

  • Mycology and Infectious Diseases
  • Pharmacology and Drug Discovery

Background:

  • Cryptococcosis, a prevalent fungal disease caused by Cryptococcus neoformans, presents a significant global health challenge with limited therapeutic options.
  • Invasive fungal infections contribute to high mortality rates, underscoring the urgent need for novel antifungal agents.

Purpose of the Study:

  • To evaluate brilacidin (BRI), a host defense peptide mimetic, as a potential antifungal agent against Cryptococcus neoformans.
  • To investigate the mechanism of action of BRI, both alone and in combination with existing antifungals, against C. neoformans.

Main Methods:

  • Assessed BRI's antifungal activity against C. neoformans and its effects on cell membrane permeability.
  • Utilized Saccharomyces cerevisiae mutant libraries to explore BRI's cellular targets.
  • Conducted in vivo studies in a murine model of invasive pulmonary cryptococcosis and evaluated BRI's synergistic effects with caspofungin (CAS).

Main Results:

  • BRI demonstrated fungicidal activity against C. neoformans, affecting cell membrane organization and increasing permeability.
  • In vivo experiments showed BRI significantly reduced C. neoformans survival in macrophages and partially cleared lung infections.
  • BRI potentiated the antifungal activity of CAS, impacting fungal endocytic movement, calcineurin, and MAPK pathways.

Conclusions:

  • Brilacidin (BRI) is a promising novel antifungal drug candidate for treating cryptococcosis.
  • BRI exhibits a multi-faceted mechanism of action, targeting fungal cell membranes and potentiating existing therapies.
Keywords:
Cryptococcus neoformansantifungal agentbrilacidincaspofungin

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