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PXD033762-1

PXD033762 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMebendazole Inhibits Histoplasma capsulatum In Vitro Growth and Decreases Mitochondrion and Cytoskeleton Protein Levels
DescriptionHistoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if treatment is unsuccessful. Itraconazole and amphotericin B are used to treat histoplasmosis; however, both antifungals have potentially severe pharmacokinetic drug interactions and toxicity. The present study determined the minimal inhibitory and fungicidal concentrations of mebendazole, a drug present in the NIH Clinical Collection, to establish whether it has fungicidal or fungistatic activity against Histoplasma capsulatum. Protein extracts from H. capsulatum yeasts, treated or not with mebendazole, were analyzed by proteomics to understand the metabolic changes driven by this benzimidazole. Mebendazole inhibited the growth of 10 H. capsulatum strains, presenting minimal inhibitory concentrations ranging from 5.0 to 0.08 µM. Proteomics revealed 30 and 18 proteins exclusively detected in untreated and mebendazole-treated H. capsulatum yeast cells, respectively. Proteins related to the tricarboxylic acid cycle, cytoskeleton, and ribosomes were highly abundant in untreated cells. Proteins related to the nitrogen, sulfur, and pyrimidine metabolisms were enriched in mebendazole-treated cells. Furthermore, mebendazole was able to inhibit the oxidative metabolism, disrupt the cytoskeleton, and decrease ribosomal proteins in H. capsulatum. These results suggest mebendazole as a drug to be repurposed for histoplasmosis treatment.
HostingRepositoryPRIDE
AnnounceDate2023-03-22
AnnouncementXMLSubmission_2023-03-22_12:19:27.969.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRichardHemmi Valente
SpeciesList scientific name: Fungi; NCBI TaxID: NCBITaxon:4751; scientific name: Histoplasma capsulatum; NCBI TaxID: 5037;
ModificationListmonohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-05-08 04:14:46ID requested
12023-03-22 12:19:28announced
22023-11-14 08:56:26announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: Histoplasma capsulatum
Mebendazole
Drug repositioning. Antifungal activity, Proteomic analysis
Contact List
Richard HemmiValente
contact affiliationLaboratory of Toxinology, FIOCRUZ, Brazil
contact emailrichardhemmi@gmail.com
lab head
RichardHemmi Valente
contact affiliationFundação Oswaldo Cruz
contact emailrichardhemmi@gmail.com
dataset submitter
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Dataset FTP location
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