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The auranofin activity against\n                      <jats:italic>Histoplasma capsulatum<\/jats:italic>\n                      , 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\n                      <jats:italic>H<\/jats:italic>\n                      .\n                      <jats:italic>capsulatum<\/jats:italic>\n                      growth and expression of virulence factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/principal findings<\/jats:title>\n                    <jats:p>\n                      Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) of auranofin against 15\n                      <jats:italic>H<\/jats:italic>\n                      .\n                      <jats:italic>capsulatum<\/jats:italic>\n                      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\n                      <jats:italic>Tenebrio molitor<\/jats:italic>\n                      invertebrate animal model. Expression of virulence-related genes was compared between auranofin treated and untreated\n                      <jats:italic>H<\/jats:italic>\n                      .\n                      <jats:italic>capsulatum<\/jats:italic>\n                      yeast cells using a quantitative PCR assay. Auranofin affected the growth of different strains of\n                      <jats:italic>H<\/jats:italic>\n                      .\n                      <jats:italic>capsulatum<\/jats:italic>\n                      , with MIC and MFC values ranging from 1.25 to 5.0 \u03bcM and from 2.5 to &gt;10 \u03bcM, respectively. Auranofin was able to kill intracellular\n                      <jats:italic>H<\/jats:italic>\n                      .\n                      <jats:italic>capsulatum<\/jats:italic>\n                      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\n                      <jats:italic>H<\/jats:italic>\n                      .\n                      <jats:italic>capsulatum<\/jats:italic>\n                      and reduces the expression of several virulence-related genes, which makes this anti-rheumatic drug a good candidate for new medicines against histoplasmosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0012586","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T13:38:23Z","timestamp":1728308303000},"page":"e0012586","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes"],"prefix":"10.1371","volume":"18","author":[{"given":"Marcos","family":"de Abreu Almeida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian Cristiane","family":"Baeza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro B. 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