PXD033762-1

PXD033762 is an original dataset announced via ProteomeXchange.

Title	Mebendazole Inhibits Histoplasma capsulatum In Vitro Growth and Decreases Mitochondrion and Cytoskeleton Protein Levels
Description	Histoplasmosis 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.
HostingRepository	PRIDE
AnnounceDate	2023-03-22
AnnouncementXML	Submission_2023-03-22_12:19:27.969.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	RichardHemmi Valente
SpeciesList	scientific name: Fungi; NCBI TaxID: NCBITaxon:4751; scientific name: Histoplasma capsulatum; NCBI TaxID: 5037;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-08 04:14:46	ID requested
⏵ 1	2023-03-22 12:19:28	announced
2	2023-11-14 08:56:26	announced	2023-11-14: Updated project metadata.

submitter keyword: Histoplasma capsulatum

Mebendazole

Drug repositioning. Antifungal activity, Proteomic analysis

Richard HemmiValente
contact affiliation	Laboratory of Toxinology, FIOCRUZ, Brazil
contact email	richardhemmi@gmail.com
lab head
RichardHemmi Valente
contact affiliation	Fundação Oswaldo Cruz
contact email	richardhemmi@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033762
     1. Label: PRIDE project
     2. Name: Mebendazole Inhibits Histoplasma capsulatum In Vitro Growth and Decreases Mitochondrion and Cytoskeleton Protein Levels