PXD070309

PXD070309 is an original dataset announced via ProteomeXchange.

Title	Cellular and molecular responses of Cryptococcus to brilacidin (MMV1634402) and KIN1400 (MMV019724)
Description	Cryptococcosis is a systemic mycosis caused by Cryptococcus neoformans and C. deuterogattii. Available therapeu-tic options are limited and face several challenges, including high toxicity, the emergence of resistant strains, high costs, and restrict-ed distribution. In this study, we evaluated the anticryptococcal potential of two compounds identified as antifungals from the Pan-demic Response Box, brilacidin (MMV1634402), a recently characterized fungicidal agent, and KIN1400 (MMV019724), an activa-tor of genes promoting antiviral responses. Both compounds exhibited inhibitory activity with minimum inhibitory concentrations (MICs) of 2.5 µM. Brilacidin demonstrated a high selectivity index (SI = 16) and low cytotoxicity in murine macrophages, whereas KIN1400 showed partial fungicidal activity and lower selectivity (SI = 2). Synergy assays revealed that brilacidin potentiated am-photericin B activity, reducing its effective dose up to eightfold without increasing cytotoxicity. Morphological analyses by scan-ning, confocal, and transmission electron microscopy confirmed previously described effects of brilacidin, in addition to profound alterations in capsule structure, plasma membrane integrity, and intracellular organization. KIN1400 induced milder, species-dependent effects, including a slight decrease in capsular size, discrete changes in cell wall organization, membrane pore formation, and intracellular alterations. These effects were more pronounced in C. neoformans than in C. deuterogattii. Brilacidin also inhibited C. neoformans biofilms, reducing metabolic activity and biomass in a concentration-dependent manner, accompanied by major structural disruption. Quantitative proteomics revealed that brilacidin and KIN1400 induced distinct, species-specific responses. Brilacidin primarily affected proteins involved in sterol metabolism, oxidative stress, and cell wall biosynthesis, while KIN1400 altered mitochondrial and RNA metabolic processes. These results provide translational knowledge for the future development of molecules with therapeutic potential against cryptococcosis.
HostingRepository	PRIDE
AnnounceDate	2026-09-09
AnnouncementXML	Submission_2026-09-09_01:56:28.454.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marlon D M Santos
SpeciesList	scientific name: Cryptococcus neoformans H99-YPD_1; NCBI TaxID: NEWT:1202347;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-04 12:10:16	ID requested
⏵ 1	2026-09-09 01:56:29	announced

10.1128/spectrum.00138-26;

Bezerra BT, Mellon DA, Souza CM, Castelli RF, Camillo-Andrade AC, Santos MDM, Carvalho PC, Rodrigues ML, Oliveira HCd, to brilacidin. Microbiol Spectr, 14(7):e0013826(2026) [pubmed]

submitter keyword: Cryptococcus neoformans, Proteomics., Biofilm, Cryptococcus deuterogattii,Cryptococcosis, Antifungal drugs Syner-gism, Antifungal activity

Haroldo C. de Oliveira
contact affiliation	Department of Microbiology, Immunology, and Parasitology, Discipline of Cellular Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
contact email	haroldo.oliveira@unifesp.br
lab head
Marlon D M Santos
contact affiliation	Computational Mass Spectrometry & Proteomics Group - Fiocruz
contact email	marlondms@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/09/PXD070309

PRIDE project URI

• PRIDE
  1. PXD070309
     1. Label: PRIDE project
     2. Name: Cellular and molecular responses of Cryptococcus to brilacidin (MMV1634402) and KIN1400 (MMV019724)