Brilacidin, a novel antifungal agent against Cryptococcus neoformans.

Diehl C, Pinzan CF, de Castro PA, Delbaje E, García Carnero LC, Sánchez-León E, Bhalla K, Kronstad JW, Kim D-g, Doering TL, Alkhazraji S, Mishra NN and 8 more

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Ibrahim AS, Yoshimura M, Vega Isuhuaylas LA, Pham LTK, Yashiroda Y, Boone C, Dos Reis TF, Goldman GH

mBio25 Jun 2024Cited by 14 (Europe PMC)

PMID38916308PMCIDPMC11253610DOI10.1128/mbio.01031-24PepBankPUB-38916308

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Summary

Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis.ImportanceInvasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

5 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with invasive pulmonary cryptococcosis, brilacidin partially cleared C. neoformans lung infection.
In plain wordsIn mice, brilacidin partially cleared Cryptococcus neoformans lung infection.
Peptide
Brilacidin
Outcome
DecreaseLung infection burden
Study
mousen: not reported in source
immunocompetent murine invasive pulmonary cryptococcosis
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis.
Show in the study text Report a problemFND-3891630804
02LabIn vitro (cells)Mechanism
In C. neoformans laboratory tests, brilacidin altered cell membrane organization and increased fungal cell permeability.
In plain wordsIn lab tests, brilacidin altered Cryptococcus neoformans cell membranes and increased their permeability.
Peptide
Brilacidin
Outcome
IncreaseCell membrane permeability
Study
Cryptococcus neoformansn: not reported in source
Cryptococcus neoformans
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
BRI can affect the organization of the cell membrane, increasing the fungal cell permeability.
Show in the study text Report a problemFND-3891630801
03LabIn vitro (cells)Mechanism
In S. cerevisiae laboratory tests, brilacidin affected membrane organization, the cell wall integrity pathway, and calcium metabolism.
In plain wordsIn lab tests, brilacidin affected yeast membrane organization, the cell wall integrity pathway, and calcium metabolism.
Peptide
Brilacidin
Outcome
Not applicableCellular pathway effects
Study
Saccharomyces cerevisiaen: not reported in source
Saccharomyces cerevisiae
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism.
Show in the study text Report a problemFND-3891630802
04LabIn vitro (cells)Activity measurement
In macrophages, brilacidin significantly reduced C. neoformans survival.
In plain wordsIn cells, brilacidin reduced Cryptococcus neoformans survival inside macrophages.
Peptide
Brilacidin
Outcome
DecreaseIntramacrophage fungal survival
Study
Cryptococcus neoformansn: not reported in source
macrophages infected with Cryptococcus neoformans
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages
Show in the study text Report a problemFND-3891630803
05LabIn vitro (cells)Activity measurement
In C. neoformans laboratory tests, brilacidin alone inhibited fungal growth and acted as a fungicidal drug.
In plain wordsIn lab tests, brilacidin alone inhibited Cryptococcus neoformans growth and killed the fungus.
Peptide
Brilacidin
Outcome
DecreaseFungicidal growth inhibition
Study
Cryptococcus neoformansn: not reported in source
Cryptococcus neoformans
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug,
Show in the study text Report a problemFND-3891630808

Studies that did not test the peptide alone3

In this study, Brilacidin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Brilacidin.

06LabNot a test of Brilacidin aloneIn vitro (cells)Mechanism
In C. neoformans laboratory tests, brilacidin with caspofungin potentiated caspofungin activity.
In plain wordsIn lab tests, brilacidin with caspofungin enhanced caspofungin activity against Cryptococcus neoformans.
Peptide
Brilacidin
Outcome
IncreaseCaspofungin potentiation
Study
Cryptococcus neoformansn: not reported in source
Cryptococcus neoformans
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans.
In this study, Brilacidin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Brilacidin.
Show in the study text Report a problemFND-3891630805
07LabNot a test of Brilacidin aloneIn vitro (cells)Mechanism
In C. neoformans laboratory tests, brilacidin with amphotericin potentiated amphotericin activity.
In plain wordsIn lab tests, brilacidin with amphotericin enhanced amphotericin activity against Cryptococcus neoformans.
Peptide
Brilacidin
Outcome
IncreaseAmphotericin potentiation
Study
Cryptococcus neoformansn: not reported in source
Cryptococcus neoformans
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans.
In this study, Brilacidin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Brilacidin.
Show in the study text Report a problemFND-3891630806
08LabNot a test of Brilacidin aloneIn vitro (cells)Mechanism
In C. neoformans laboratory tests, brilacidin plus caspofungin affected endocytic movement, calcineurin, and mitogen-activated protein kinases.
In plain wordsIn lab tests, brilacidin plus caspofungin affected fungal endocytic movement, calcineurin, and mitogen-activated protein kinases.
Peptide
Brilacidin
Outcome
Not applicableCombination pathway effects
Study
Cryptococcus neoformansn: not reported in source
Cryptococcus neoformans
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases.
In this study, Brilacidin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Brilacidin.
Show in the study text Report a problemFND-3891630807

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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