Auranofin is active against Histoplasma capsulatum and reduces the expression of virulence-related genes

被引：0

作者：

Almeida, Marcos de Abreu ^{[1
,2
]}

Baeza, Lilian Cristiane ^{[3
]}

Silva, Leandro B. R. ^{[4
,5
]}

Bernardes-Engemann, Andrea Reis ^{[1
]}

Almeida-Silva, Fernando ^{[1
]}

Coelho, Rowena Alves ^{[1
]}

de Andrade, Iara Bastos ^{[6
]}

Correa-Junior, Dario ^{[6
]}

Frases, Susana ^{[6
,7
]}

Zancope-Oliveira, Rosely Maria ^{[1
]}

Alanio, Alexandre ^{[8
]}

Taborda, Carlos Pelleschi ^{[4
]}

Almeida-Paes, Rodrigo ^{[1
,7
]}

机构：

[1] Fundacao Oswaldo Cruz, Lab Micol, Inst Nacl Infectol Evandro Chagas, Rio De Janeiro, Brazil

[2] Univ Fed Fluminense, Dept Microbiol & Parasitol, Inst Biomed, Niteroi, Brazil

[3] Univ Estadual Oeste Parana, Ctr Ciencias Med & Farmaceut, Cascavel, Brazil

[4] Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, Sao Paulo, Brazil

[5] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC, Canada

[6] Univ Fed Rio de Janeiro, Lab Biofis Fungos, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, Brazil

[7] FAPERJ, Rede Micol, Rio De Janeiro, Brazil

[8] Univ Paris Cite, Inst Pasteur, Ctr Natl Reference Mycoses Invas & Antifong, Dept Mycol,Grp Rech Mycol Translat, Paris, France

来源：

PLOS NEGLECTED TROPICAL DISEASES | 2024年 / 18卷 / 10期

关键词：

ANTIFUNGAL; MODELS;

D O I：

10.1371/journal.pntd.0012586

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

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 mu M and from 2.5 to >10 mu M, 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.

引用

页数：16