Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes
Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) of auranofin against 15 H. capsulatum strains with distinct genetic backgrounds were determined using the yeast form of the fungus and a microdilution protocol. Auranofin activity was also assessed on a macrophage model of infection and on a Tenebrio molitor invertebrate animal model. Expression of virulence-related genes was compared between auranofin treated and untreated H. capsulatum yeast cells using a quantitative PCR assay. Auranofin affected the growth of different strains of H. capsulatum, with MIC and MFC values ranging from 1.25 to 5.0 μM and from 2.5 to >10 μM, respectively. Auranofin was able to kill intracellular H. capsulatum yeast cells and conferred protection against the fungus in the experimental animal model of infection. Moreover, the expression of catalase A, HSP70, superoxide dismutase, thioredoxin reductase, serine proteinase, cytochrome C peroxidase, histone 2B, formamidase, metallopeptidase, Y20 and YPS3 proteins were reduced after six hours of auranofin treatment. CONCLUSIONS/SIGNIFICANCE: Auranofin is fungicidal against H. capsulatum and reduces the expression of several virulence-related genes, which makes this anti-rheumatic drug a good candidate for new medicines against histoplasmosis.
Authors
- Carlos P. Taborda (ORCID: https://orcid.org/0000-0001-9928-9809)
- Iara Bastos de Andrade (ORCID: https://orcid.org/0000-0002-4730-0815)
- Rosely Maria Zancopé‐Oliveira (ORCID: https://orcid.org/0000-0001-7619-1921)
- Marcos de Abreu Almeida (ORCID: https://orcid.org/0000-0002-5581-631X)
- Leandro Buffoni Roque da Silva (ORCID: https://orcid.org/0000-0001-6545-5725)
- Dario Corrêa-Junior (ORCID: https://orcid.org/0000-0003-2821-4978)
- Andréa Reis Bernardes‐Engemann (ORCID: https://orcid.org/0000-0002-4997-8734)
- Rowena Alves Coelho (ORCID: https://orcid.org/0000-0002-4255-7486)
- Fernando Almeida‐Silva (ORCID: https://orcid.org/0000-0002-7378-1990)
- Alexandre Alanio (ORCID: https://orcid.org/0000-0001-9726-3082)
- Lílian Cristiane Baeza (ORCID: https://orcid.org/0000-0003-4119-9573)
- Rodrigo Almeida‐Paes (ORCID: https://orcid.org/0000-0002-6639-6058)
- Susana Frasés (ORCID: https://orcid.org/0000-0001-5875-9886)
Institutions
- Universidade Federal do Rio de Janeiro (BR)
- University of British Columbia (CA)
- Institut Pasteur (FR)
- Universidade Federal Fluminense (BR)
- Universidade de São Paulo (BR)
- Universidade Estadual do Oeste do Paraná (BR)
- Université Paris Cité (FR)
- Instituto Evandro Chagas (BR)
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (BR)
- Fundação Oswaldo Cruz (BR)
Publication Details
- Journal
- PLoS neglected tropical diseases
- Published
- 2024-10-07
- DOI
- https://doi.org/10.1371/journal.pntd.0012586
- Citations
- 3
- Primary Topic
- Fungal Infections and Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro