Cellular and molecular responses of Cryptococcus to brilacidin.

Bezerra BT, Mellon DA, Souza CM, Castelli RF, Camillo-Andrade AC, Santos MDM, Carvalho PC, Rodrigues ML, Oliveira HCd

Microbiology spectrum15 Jun 2026

PMID42294727PMCIDPMC13340292DOI10.1128/spectrum.00138-26PepBankPUB-42294727

Summary

Cryptococcosis is a systemic mycosis caused by Cryptococcus neoformans and Cryptococcus deuterogattii. Available therapeutic options are limited and face several challenges, including toxicity, the emergence of resistant strains, high costs, and restricted distribution. In this study, we explored the cellular and molecular responses of Cryptococcus spp. to brilacidin, a recently characterized fungicidal agent with promising potential for the treatment of cryptococcosis. Brilacidin exhibited inhibitory activity with a minimum inhibitory concentration of 2.5 µM and demonstrated a high selectivity index and low cytotoxicity in murine macrophages. Synergy assays revealed that brilacidin potentiated amphotericin B activity, reducing its effective dose up to eightfold without increasing cytotoxicity. Morphological analyses by scanning, confocal, and transmission electron microscopy expanded previously described effects of brilacidin and revealed profound alterations in capsule structure, plasma membrane integrity, and intracellular organization. Brilacidin also inhibited C. neoformans biofilms in a concentration-dependent manner, accompanied by major structural disruption. We investigated the molecular response of C. neoformans and C. deuterogattii to brilacidin by quantitative proteomics, which revealed species-specific responses. Brilacidin primarily affected proteins involved in sterol metabolism, oxidative stress, and cell wall biosynthesis. These results deepen our understanding of the anti-Cryptococcus effects of brilacidin and reinforce the potential of this drug as a highly promising antifungal agent for the treatment of cryptococcosis.IMPORTANCECryptococcosis is a life-threatening fungal disease that mainly affects immunocompromised individuals and remains difficult to treat due to toxic drugs, limited therapeutic options, and the emergence of resistance. This study deepens the understanding of brilacidin as a promising antifungal candidate against the causative agents of cryptococcosis. Brilacidin exhibits potent fungicidal activity at low concentrations with minimal toxicity to host cells and enhances the efficacy of amphotericin B, allowing for reduced doses that may mitigate adverse effects. Furthermore, brilacidin disrupts key fungal structures, including the capsule and biofilms, and induces distinct cellular stress responses. By providing mechanistic and translational insights, this work supports the development of safer and more effective therapeutic strategies for this neglected and often fatal fungal infection.

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

Results from this study8

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

01LabIn vitro (cells)Activity measurement
In Cryptococcus laboratory tests, brilacidin had a minimum inhibitory concentration of 2.5 µM.
In plain wordsIn lab tests, brilacidin inhibited Cryptococcus at 2.5 µM.
Peptide
Brilacidin
Outcome
Not applicableMinimum inhibitory concentration
Study
n: not reported in source
Cryptococcus spp.
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Measurements
MIC
2.5 µM
Cryptococcus
Source sentences
Summary
Brilacidin exhibited inhibitory activity with a minimum inhibitory concentration of 2.5 µM and demonstrated a high selectivity index and low cytotoxicity in murine macrophages.
Show in the study text Report a problemFND-4229472701
02LabIn vitro (cells)Activity measurement
In laboratory tests, brilacidin showed a high selectivity index.
In plain wordsIn lab tests, brilacidin showed a high selectivity index.
Peptide
Brilacidin
Outcome
Not applicableSelectivity index
Study
n: not reported in source
Cryptococcus spp.
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
Brilacidin exhibited inhibitory activity with a minimum inhibitory concentration of 2.5 µM and demonstrated a high selectivity index and low cytotoxicity in murine macrophages.
Show in the study text Report a problemFND-4229472702
03LabIn vitro (cells)Safety outcome
In murine macrophages, brilacidin showed low cytotoxicity.
In plain wordsIn cells from mice, brilacidin showed low toxicity.
Peptide
Brilacidin
Outcome
Not applicableMacrophage cytotoxicity
Study
mousen: not reported in source
murine macrophages
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Brilacidin exhibited inhibitory activity with a minimum inhibitory concentration of 2.5 µM and demonstrated a high selectivity index and low cytotoxicity in murine macrophages.
Show in the study text Report a problemFND-4229472703
04LabIn vitro (cells)Mechanism
In Cryptococcus laboratory tests, brilacidin altered capsule structure, plasma membrane integrity, and intracellular organization.
In plain wordsIn lab tests, brilacidin altered Cryptococcus capsule structure, membrane integrity, and internal organization.
Peptide
Brilacidin
Outcome
Not applicableFungal cellular morphology
Study
n: not reported in source
Cryptococcus spp.
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
Morphological analyses by scanning, confocal, and transmission electron microscopy expanded previously described effects of brilacidin and revealed profound alterations in capsule structure, plasma membrane integrity, and intracellular organization.
Show in the study text Report a problemFND-4229472706
05LabIn vitro (cells)Activity measurement
In laboratory tests, brilacidin inhibited C. neoformans biofilms in a concentration-dependent manner with major structural disruption.
In plain wordsIn lab tests, brilacidin inhibited Cryptococcus neoformans biofilms as concentration increased and disrupted their structure.
Peptide
Brilacidin
Outcome
DecreaseBiofilm inhibition
Study
n: not reported in source
Cryptococcus neoformans biofilms
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
Brilacidin also inhibited C. neoformans biofilms in a concentration-dependent manner, accompanied by major structural disruption.
Show in the study text Report a problemFND-4229472707
06LabIn vitro (cells)Mechanism
In Cryptococcus laboratory tests, brilacidin elicited species-specific proteomic responses affecting sterol metabolism, oxidative stress, and cell wall biosynthesis proteins.
In plain wordsIn lab tests, Cryptococcus species showed different protein responses to brilacidin.
Peptide
Brilacidin
Outcome
Not applicableProteomic response
Study
n: not reported in source
Cryptococcus spp.
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated
Source sentences
Summary
We investigated the molecular response of C. neoformans and C. deuterogattii to brilacidin by quantitative proteomics, which revealed species-specific responses.
1 context sentence(design, population, supporting numbers)
Summary · context
Brilacidin primarily affected proteins involved in sterol metabolism, oxidative stress, and cell wall biosynthesis.
Show in the study text Report a problemFND-4229472708

Studies that did not test the peptide alone2

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.

07LabNot a test of Brilacidin aloneIn vitro (cells)Activity measurement
In Cryptococcus laboratory tests, brilacidin plus amphotericin B reduced the effective amphotericin B dose up to eightfold.
In plain wordsIn lab tests, brilacidin plus amphotericin B reduced the effective amphotericin B dose up to eightfold.
Peptide
Brilacidin
Outcome
IncreaseAmphotericin B potentiation
Study
n: not reported in source
Cryptococcus spp.
Outcome group
Infection and antimicrobial activity · Infection
Measurements
Effective amphotericin B dose reduction
8 fold
up to eightfold with brilacidin
Source sentences
Summary
Synergy assays revealed that brilacidin potentiated amphotericin B activity, reducing its effective dose up to eightfold without increasing cytotoxicity.
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-4229472704
08LabNot a test of Brilacidin aloneIn vitro (cells)Safety outcome
In laboratory synergy assays, brilacidin plus amphotericin B did not increase cytotoxicity.
In plain wordsIn lab tests, brilacidin plus amphotericin B did not increase cell toxicity.
Peptide
Brilacidin
Outcome
Not applicableCombination cytotoxicity
Study
n: not reported in source
Cryptococcus spp.
Outcome group
Adverse events · Whole body
Source sentences
Summary
Synergy assays revealed that brilacidin potentiated amphotericin B activity, reducing its effective dose up to eightfold without increasing cytotoxicity.
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-4229472705

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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