Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone®) as a Chemotherapeutic Candidate for the Treatment of Cryptococcus neoformans Infection

Author:

Alves Vinicius1ORCID,Martins Pedro Henrique1,Miranda Bruna1,de Andrade Iara Bastos1ORCID,Pereira Luiza1,Maeda Christina Takiya2,de Sousa Araújo Glauber Ribeiro1ORCID,Frases Susana13ORCID

Affiliation:

1. Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil

2. Laboratório de Fisiopatologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil

3. Rede Micologia RJ, FAPERJ, Rio de Janeiro 21941-902, Brazil

Abstract

Cryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various Cryptococcus species. The current treatment utilizes a combination of antifungal drugs, but issues such as nephrotoxicity, restricted or limited availability in certain countries, and resistance limit their effectiveness. Repurposing approved drugs presents a viable strategy for developing new antifungal options. This study investigates the potential of glatiramer acetate (Copaxone®) as a chemotherapy candidate for Cryptococcus neoformans infection. Various techniques are employed to evaluate the effects of glatiramer acetate on the fungus, including microdilution, XTT analysis, electron and light microscopy, and physicochemical measurements. The results demonstrate that glatiramer acetate exhibits antifungal properties, with an IC50 of 0.470 mg/mL and a minimum inhibitory concentration (MIC) of 2.5 mg/mL. Furthermore, it promotes enhanced cell aggregation, facilitates biofilm formation, and increases the secretion of fungal polysaccharides. These findings indicate that glatiramer acetate not only shows an antifungal effect but also modulates the key virulence factor—the polysaccharide capsule. In summary, repurposing glatiramer acetate as a potential chemotherapy option offers new prospects for combating C. neoformans infection. It addresses the limitations associated with current antifungal therapies by providing an alternative treatment approach.

Funder

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro—Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil

Publisher

MDPI AG

Subject

Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)

Reference63 articles.

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2. Innate Immunity in the Lungs;Martin;Proc. Am. Thorac. Soc.,2005

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4. Cryptococcosis in the Immunocompetent Patient;Goldman;Respir. Care,2010

5. Titan Cells in Cryptococcus neoformans: Cells with a Giant Impact;Zaragoza;Curr. Opin. Microbiol.,2013

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