Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone<sup>®</sup>) as a Chemotherapeutic Candidate for the Treatment of <i>Cryptococcus neoformans</i> Infection
Cryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various <i>Cryptococcus</i> species. The current treatment utilizes a combination of antifungal drugs, but issues such as nephrotoxicity, restricted or limited availability in certain countries, and re...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Journal of Fungi |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2309-608X/9/8/783 |
| _version_ | 1797584185785843712 |
|---|---|
| author | Vinicius Alves Pedro Henrique Martins Bruna Miranda Iara Bastos de Andrade Luiza Pereira Christina Takiya Maeda Glauber Ribeiro de Sousa Araújo Susana Frases |
| author_facet | Vinicius Alves Pedro Henrique Martins Bruna Miranda Iara Bastos de Andrade Luiza Pereira Christina Takiya Maeda Glauber Ribeiro de Sousa Araújo Susana Frases |
| author_sort | Vinicius Alves |
| collection | DOAJ |
| description | Cryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various <i>Cryptococcus</i> 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<sup>®</sup>) as a chemotherapy candidate for <i>Cryptococcus neoformans</i> 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 IC<sub>50</sub> 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 <i>C. neoformans</i> infection. It addresses the limitations associated with current antifungal therapies by providing an alternative treatment approach. |
| first_indexed | 2024-03-10T23:49:30Z |
| format | Article |
| id | doaj.art-68d861dd32014bf583a25b732e70260c |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-10T23:49:30Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-68d861dd32014bf583a25b732e70260c2023-11-19T01:46:57ZengMDPI AGJournal of Fungi2309-608X2023-07-019878310.3390/jof9080783Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone<sup>®</sup>) as a Chemotherapeutic Candidate for the Treatment of <i>Cryptococcus neoformans</i> InfectionVinicius Alves0Pedro Henrique Martins1Bruna Miranda2Iara Bastos de Andrade3Luiza Pereira4Christina Takiya Maeda5Glauber Ribeiro de Sousa Araújo6Susana Frases7Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Fisiopatologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilCryptococcosis is a systemic mycosis affecting immunosuppressed individuals, caused by various <i>Cryptococcus</i> 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<sup>®</sup>) as a chemotherapy candidate for <i>Cryptococcus neoformans</i> 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 IC<sub>50</sub> 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 <i>C. neoformans</i> infection. It addresses the limitations associated with current antifungal therapies by providing an alternative treatment approach.https://www.mdpi.com/2309-608X/9/8/783<i>Cryptococcus neoformans</i>cryptococcosisdrug repositioningpolysaccharide capsule |
| spellingShingle | Vinicius Alves Pedro Henrique Martins Bruna Miranda Iara Bastos de Andrade Luiza Pereira Christina Takiya Maeda Glauber Ribeiro de Sousa Araújo Susana Frases Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone<sup>®</sup>) as a Chemotherapeutic Candidate for the Treatment of <i>Cryptococcus neoformans</i> Infection Journal of Fungi <i>Cryptococcus neoformans</i> cryptococcosis drug repositioning polysaccharide capsule |
| title | Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone<sup>®</sup>) as a Chemotherapeutic Candidate for the Treatment of <i>Cryptococcus neoformans</i> Infection |
| title_full | Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone<sup>®</sup>) as a Chemotherapeutic Candidate for the Treatment of <i>Cryptococcus neoformans</i> Infection |
| title_fullStr | Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone<sup>®</sup>) as a Chemotherapeutic Candidate for the Treatment of <i>Cryptococcus neoformans</i> Infection |
| title_full_unstemmed | Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone<sup>®</sup>) as a Chemotherapeutic Candidate for the Treatment of <i>Cryptococcus neoformans</i> Infection |
| title_short | Assessing the In Vitro Potential of Glatiramer Acetate (Copaxone<sup>®</sup>) as a Chemotherapeutic Candidate for the Treatment of <i>Cryptococcus neoformans</i> Infection |
| title_sort | assessing the in vitro potential of glatiramer acetate copaxone sup r sup as a chemotherapeutic candidate for the treatment of i cryptococcus neoformans i infection |
| topic | <i>Cryptococcus neoformans</i> cryptococcosis drug repositioning polysaccharide capsule |
| url | https://www.mdpi.com/2309-608X/9/8/783 |
| work_keys_str_mv | AT viniciusalves assessingtheinvitropotentialofglatirameracetatecopaxonesupsupasachemotherapeuticcandidateforthetreatmentoficryptococcusneoformansiinfection AT pedrohenriquemartins assessingtheinvitropotentialofglatirameracetatecopaxonesupsupasachemotherapeuticcandidateforthetreatmentoficryptococcusneoformansiinfection AT brunamiranda assessingtheinvitropotentialofglatirameracetatecopaxonesupsupasachemotherapeuticcandidateforthetreatmentoficryptococcusneoformansiinfection AT iarabastosdeandrade assessingtheinvitropotentialofglatirameracetatecopaxonesupsupasachemotherapeuticcandidateforthetreatmentoficryptococcusneoformansiinfection AT luizapereira assessingtheinvitropotentialofglatirameracetatecopaxonesupsupasachemotherapeuticcandidateforthetreatmentoficryptococcusneoformansiinfection AT christinatakiyamaeda assessingtheinvitropotentialofglatirameracetatecopaxonesupsupasachemotherapeuticcandidateforthetreatmentoficryptococcusneoformansiinfection AT glauberribeirodesousaaraujo assessingtheinvitropotentialofglatirameracetatecopaxonesupsupasachemotherapeuticcandidateforthetreatmentoficryptococcusneoformansiinfection AT susanafrases assessingtheinvitropotentialofglatirameracetatecopaxonesupsupasachemotherapeuticcandidateforthetreatmentoficryptococcusneoformansiinfection |