Related Experiment Video
Updated: Jun 11, 2025
Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes
Marcos de Abreu Almeida1,2, Lilian Cristiane Baeza3, Leandro B R Silva4,5
1Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Background:
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.
Methodology/Principal Findings:
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.
Insights
The anti-rheumatic drug auranofin effectively inhibits the growth of Histoplasma capsulatum, the fungus causing histoplasmosis. Auranofin also reduces key virulence factors, suggesting its potential as a novel antifungal treatment.
Area of Science:
- Mycology
- Antimicrobial drug discovery
- Infectious diseases
Background:
- Auranofin is an established anti-rheumatic medication with known antimicrobial properties.
- Its efficacy against Histoplasma capsulatum, a fungus causing severe systemic mycosis, remains largely uninvestigated.
- Limited therapeutic options exist for histoplasmosis, highlighting the need for new treatments.
Purpose of the Study:
- To evaluate the antifungal activity of auranofin against Histoplasma capsulatum.
- To assess the impact of auranofin on H. capsulatum virulence factor expression.
Main Methods:
- Determined minimal inhibitory and fungicidal concentrations (MIC and MFC) of auranofin against 15 H. capsulatum strains.
- Assessed auranofin's efficacy in macrophage and Tenebrio molitor infection models.
- Quantified changes in virulence gene expression using quantitative PCR.
Main Results:
- Auranofin demonstrated fungicidal activity against H. capsulatum, with MICs ranging from 1.25 to 5.0 μM and MFCs from 2.5 to >10 μM.
- Auranofin reduced intracellular fungal burden and provided protection in an animal model.
- Expression of multiple virulence-related genes, including catalase A and HSP70, was significantly decreased.
Conclusions:
- Auranofin exhibits potent fungicidal activity against H. capsulatum.
- Auranofin effectively reduces the expression of key virulence factors in H. capsulatum.
- Auranofin represents a promising candidate for developing novel therapeutics against histoplasmosis.
Related Concept Videos
01:28Gene Regulation in Microbial Communities: Quorum Sensing
01:28Antimicrobial Effectiveness