Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes.
<h4>Background</h4>Auranofin is an approved anti-rheumatic drug that has a broad-range inhibitory action against several microorganisms, including human pathogenic fungi. The auranofin activity against Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, has not been...
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Public Library of Science (PLoS)
2024-10-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0012586 |
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| author | Marcos de Abreu Almeida Lilian Cristiane Baeza Leandro B R Silva Andréa Reis Bernardes-Engemann Fernando Almeida-Silva Rowena Alves Coelho Iara Bastos de Andrade Dario Corrêa-Junior Susana Frases Rosely Maria Zancopé-Oliveira Alexandre Alanio Carlos Pelleschi Taborda Rodrigo Almeida-Paes |
| author_facet | Marcos de Abreu Almeida Lilian Cristiane Baeza Leandro B R Silva Andréa Reis Bernardes-Engemann Fernando Almeida-Silva Rowena Alves Coelho Iara Bastos de Andrade Dario Corrêa-Junior Susana Frases Rosely Maria Zancopé-Oliveira Alexandre Alanio Carlos Pelleschi Taborda Rodrigo Almeida-Paes |
| author_sort | Marcos de Abreu Almeida |
| collection | DOAJ |
| description | <h4>Background</h4>Auranofin is an approved anti-rheumatic drug that has a broad-range inhibitory action against several microorganisms, including human pathogenic fungi. The auranofin activity against Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, has not been properly addressed. Since there are few therapeutic options for this life-threatening systemic mycosis, this study evaluated the effects of auranofin on H. capsulatum growth and expression of virulence factors.<h4>Methodology/principal findings</h4>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. |
| format | Article |
| id | doaj-art-3326d577efa344599d496e6620ea7614 |
| institution | OA Journals |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-3326d577efa344599d496e6620ea76142025-08-20T01:57:26ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352024-10-011810e001258610.1371/journal.pntd.0012586Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes.Marcos de Abreu AlmeidaLilian Cristiane BaezaLeandro B R SilvaAndréa Reis Bernardes-EngemannFernando Almeida-SilvaRowena Alves CoelhoIara Bastos de AndradeDario Corrêa-JuniorSusana FrasesRosely Maria Zancopé-OliveiraAlexandre AlanioCarlos Pelleschi TabordaRodrigo Almeida-Paes<h4>Background</h4>Auranofin is an approved anti-rheumatic drug that has a broad-range inhibitory action against several microorganisms, including human pathogenic fungi. The auranofin activity against Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, has not been properly addressed. Since there are few therapeutic options for this life-threatening systemic mycosis, this study evaluated the effects of auranofin on H. capsulatum growth and expression of virulence factors.<h4>Methodology/principal findings</h4>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.https://doi.org/10.1371/journal.pntd.0012586 |
| spellingShingle | Marcos de Abreu Almeida Lilian Cristiane Baeza Leandro B R Silva Andréa Reis Bernardes-Engemann Fernando Almeida-Silva Rowena Alves Coelho Iara Bastos de Andrade Dario Corrêa-Junior Susana Frases Rosely Maria Zancopé-Oliveira Alexandre Alanio Carlos Pelleschi Taborda Rodrigo Almeida-Paes Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes. PLoS Neglected Tropical Diseases |
| title | Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes. |
| title_full | Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes. |
| title_fullStr | Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes. |
| title_full_unstemmed | Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes. |
| title_short | Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes. |
| title_sort | auranofin is active against histoplasma capsulatum and reduces the expression of virulence related genes |
| url | https://doi.org/10.1371/journal.pntd.0012586 |
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