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4. In vitro isavuconazole activity against Sporothrix brasiliensis suggests its efficacy in some severe sporotrichosis cases

Author

Almeida-Silva, Fernando, primary, Coelho, Rowena A, additional, Bernardes-Engemann, Andréa R, additional, Fichman, Vivian, additional, Freitas, Dayvison FS, additional, Galhardo, Maria CG, additional, Corrêa-Junior, Dario, additional, Frases, Susana, additional, Zancopé-Oliveira, Rosely M, additional, and Almeida-Paes, Rodrigo, additional

Published
2023
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5. Metabolic Plasticity and Virulence-Associated Factors of Sporothrix brasiliensis Strains Related to Familiar Outbreaks of Cat-to-Human Transmitted Sporotrichosis

Author

Corrêa-Junior, Dario, primary, de Andrade, Iara Bastos, additional, Alves, Vinicius, additional, Avellar-Moura, Igor, additional, Rodrigues-Alves, Tânia, additional, de Souza Rabello, Vanessa Brito, additional, de S. Araújo, Glauber R., additional, Borba-Santos, Luana Pereira, additional, Zancopé-Oliveira, Rosely Maria, additional, Almeida-Paes, Rodrigo, additional, and Frases, Susana, additional

Published
2023
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6. Unveiling the Morphostructural Plasticity of Zoonotic Sporotrichosis Fungal Strains: Possible Implications for Sporothrix brasiliensis Virulence and Pathogenicity

Author

Corrêa-Junior, Dario, primary, Bastos de Andrade, Iara, additional, Alves, Vinicius, additional, Avellar-Moura, Igor, additional, Brito de Souza Rabello, Vanessa, additional, Valdez, Alessandro Fernandes, additional, Nimrichter, Leonardo, additional, Zancopé-Oliveira, Rosely Maria, additional, Ribeiro de Sousa Araújo, Glauber, additional, Almeida-Paes, Rodrigo, additional, and Frases, Susana, additional

Published
2023
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7. Cyclosporine Affects the Main Virulence Factors of Cryptococcus neoformans In Vitro

Author

Andrade, Iara Bastos de, primary, Corrêa-Junior, Dario, additional, Alves, Vinicius, additional, Figueiredo-Carvalho, Maria Helena Galdino, additional, Santos, Marcos Vinicius, additional, Almeida, Marcos Abreu, additional, Valdez, Alessandro Fernandes, additional, Nimrichter, Leonardo, additional, Almeida-Paes, Rodrigo, additional, and Frases, Susana, additional

Published
2023
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8. Mebendazole Inhibits Histoplasma capsulatum In Vitro Growth and Decreases Mitochondrion and Cytoskeleton Protein Levels

Author

Almeida, Marcos Abreu, primary, Bernardes-Engemann, Andrea Reis, additional, Coelho, Rowena Alves, additional, Lugones, Camila Jantoro Guzman, additional, de Andrade, Iara Bastos, additional, Corrêa-Junior, Dario, additional, de Oliveira, Simone Santiago Carvalho, additional, dos Santos, André Luis Souza, additional, Frases, Susana, additional, Rodrigues, Márcio Lourenço, additional, Valente, Richard Hemmi, additional, Zancopé-Oliveira, Rosely Maria, additional, and Almeida-Paes, Rodrigo, additional

Published
2023
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10. In VitroIsavuconazole Activity Against Sporothrix BrasiliensisSuggests Its Efficacy in Some Severe Sporotrichosis Cases

Author

Almeida-Silva, Fernando, Coelho, Rowena A, Bernardes-Engemann, Andréa R, Fichman, Vivian, Freitas, Dayvison FS, Galhardo, Maria CG, Corrêa-Junior, Dario, Frases, Susana, Zancopé-Oliveira, Rosely M, and Almeida-Paes, Rodrigo

Abstract

Background:Sporothrix brasiliensiscauses sporotrichosis, an important infection in some groups of patients. Aims:This work was designed to investigate the effects of isavuconazole against this species. Methods:An antifungal susceptibility test was performed to compare MIC values with other antifungal drugs used to treat sporotrichosis. A checkerboard assay was performed to understand isavuconazole interactions. Furthermore, isavuconazole growth inhibition on an itraconazole-resistant strain was tested. Results:Isavuconazole had similar MICs to other azoles against S. brasiliensis, presenting fungistatic activity. Isavuconazole did not interact in vitrowith antifungals or immunosuppressive drugs and inhibited the growth of an itraconazole-resistant strain. Conclusion:Isavuconazole inhibits S. brasiliensis, its pharmacologic characteristics make it a candidate for patients with sporotrichosis and it may be useful to combat sporotrichosis caused by resistant isolates.

Published
2023
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11. Cyclosporine Affects the Main Virulence Factors of Cryptococcus neoformans In Vitro.

Author

de Andrade, Iara Bastos, Corrêa-Junior, Dario, Alves, Vinicius, Figueiredo-Carvalho, Maria Helena Galdino, Santos, Marcos Vinicius, Almeida, Marcos Abreu, Valdez, Alessandro Fernandes, Nimrichter, Leonardo, Almeida-Paes, Rodrigo, and Frases, Susana

Subjects
*CRYPTOCOCCUS neoformans, *CYCLOSPORINE, *CHITIN, *ANTIFUNGAL agents, *FUNGAL cell walls, *POLYSACCHARIDES, *CELL metabolism
Abstract

This study aimed to investigate the effects of cyclosporine on the morphology, cell wall structure, and secretion characteristics of Cryptococcus neoformans. The minimum inhibitory concentration (MIC) of cyclosporine was found to be 2 µM (2.4 µg/mL) for the H99 strain. Yeast cells treated with cyclosporine at half the MIC showed altered morphology, including irregular shapes and elongated projections, without an effect on cell metabolism. Cyclosporine treatment resulted in an 18-fold increase in chitin and an 8-fold increase in lipid bodies, demonstrating changes in the fungal cell wall structure. Cyclosporine also reduced cell body and polysaccharide capsule diameters, with a significant reduction in urease secretion in C. neoformans cultures. Additionally, the study showed that cyclosporine increased the viscosity of secreted polysaccharides and reduced the electronegativity and conductance of cells. The findings suggest that cyclosporine has significant effects on C. neoformans morphology, cell wall structure, and secretion, which could have implications for the development of new antifungal agents. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Mebendazole Inhibits Histoplasma capsulatum In Vitro Growth and Decreases Mitochondrion and Cytoskeleton Protein Levels.

Author

Abreu Almeida, Marcos, Bernardes-Engemann, Andrea Reis, Alves Coelho, Rowena, Guzman Lugones, Camila Jantoro, Bastos de Andrade, Iara, Corrêa-Junior, Dario, Carvalho de Oliveira, Simone Santiago, Souza dos Santos, André Luis, Frases, Susana, Lourenço Rodrigues, Márcio, Hemmi Valente, Richard, Zancopé-Oliveira, Rosely Maria, and Almeida-Paes, Rodrigo

Subjects
RIBOSOMES, ITRACONAZOLE, KREBS cycle, CYTOSKELETON, RIBOSOMAL proteins, MITOCHONDRIA, HIV-positive persons
Abstract

Histoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if treatment is unsuccessful. Itraconazole and amphotericin B are used to treat histoplasmosis; however, both antifungals have potentially severe pharmacokinetic drug interactions and toxicity. The present study determined the minimal inhibitory and fungicidal concentrations of mebendazole, a drug present in the NIH Clinical Collection, to establish whether it has fungicidal or fungistatic activity against Histoplasma capsulatum. Protein extracts from H. capsulatum yeasts, treated or not with mebendazole, were analyzed by proteomics to understand the metabolic changes driven by this benzimidazole. Mebendazole inhibited the growth of 10 H. capsulatum strains, presenting minimal inhibitory concentrations ranging from 5.0 to 0.08 µM. Proteomics revealed 30 and 18 proteins exclusively detected in untreated and mebendazole-treated H. capsulatum yeast cells, respectively. Proteins related to the tricarboxylic acid cycle, cytoskeleton, and ribosomes were highly abundant in untreated cells. Proteins related to the nitrogen, sulfur, and pyrimidine metabolisms were enriched in mebendazole-treated cells. Furthermore, mebendazole was able to inhibit the oxidative metabolism, disrupt the cytoskeleton, and decrease ribosomal proteins in H. capsulatum. These results suggest mebendazole as a drug to be repurposed for histoplasmosis treatment. [ABSTRACT FROM AUTHOR]

Published
2023
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