Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The <i>Fonsecaea</i>/Micafungin Paradigm
Several human pathogenic fungi produce melanin. One of its properties during parasitism is the protection against antifungal drugs. This occurs with the agents of chromoblastomycosis, in which DHN-melanin reduces antifungal susceptibility to terbinafine and itraconazole. Since these agents are resis...
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MDPI AG
2022-05-01
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| Series: | Microbiology Research |
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| Online Access: | https://www.mdpi.com/2036-7481/13/2/17 |
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| author | Rowena Alves Coelho Maria Helena Galdino Figueiredo-Carvalho Juliana Vitória dos Santos Silva Dario Correa-Junior Susana Frases Rosely Maria Zancopé-Oliveira Dayvison Francis Saraiva Freitas Rodrigo Almeida-Paes |
| author_facet | Rowena Alves Coelho Maria Helena Galdino Figueiredo-Carvalho Juliana Vitória dos Santos Silva Dario Correa-Junior Susana Frases Rosely Maria Zancopé-Oliveira Dayvison Francis Saraiva Freitas Rodrigo Almeida-Paes |
| author_sort | Rowena Alves Coelho |
| collection | DOAJ |
| description | Several human pathogenic fungi produce melanin. One of its properties during parasitism is the protection against antifungal drugs. This occurs with the agents of chromoblastomycosis, in which DHN-melanin reduces antifungal susceptibility to terbinafine and itraconazole. Since these agents are resistant to some antifungal drugs, we investigated the role of DHN-melanin on the <i>Fonsecaea</i> susceptibility to amphotericin B, micafungin, fluconazole, and flucytosine, drugs that usually present high minimal inhibitory concentrations (MIC) to this genus. Seven strains from three <i>Fonsecaea</i> human pathogenic species were treated with tricyclazole, a DHN-melanin inhibitor, and the MIC of the treated and untreated cells were compared. A survival assay was performed to confirm the alterations in the susceptibility of strains with reduced melanization, and the chitin levels of the strains were estimated by fluorescence. Tricyclazole did not affect fluconazole and flucytosine MIC, while melanin inhibition increased susceptibility to amphotericin B. Surprisingly, DHN-melanin inhibition decreased the susceptibility to micafungin. Survival assays confirmed this result on five strains. Cell wall chitin levels of the strains were not associated with the decrease in micafungin susceptibility. The results show that DHN-melanin does not have a role in the intrinsic resistance of <i>Fonseacaea</i> spp. to amphotericin B, fluconazole, and flucytosine, and its inhibition may promote micafungin resistance. |
| first_indexed | 2024-03-09T23:02:10Z |
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| last_indexed | 2024-03-09T23:02:10Z |
| publishDate | 2022-05-01 |
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| spelling | doaj.art-a2ce22cd805b4b88ba1ded1eda5c7a792023-11-23T17:59:39ZengMDPI AGMicrobiology Research2036-74812022-05-0113220120910.3390/microbiolres13020017Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The <i>Fonsecaea</i>/Micafungin ParadigmRowena Alves Coelho0Maria Helena Galdino Figueiredo-Carvalho1Juliana Vitória dos Santos Silva2Dario Correa-Junior3Susana Frases4Rosely Maria Zancopé-Oliveira5Dayvison Francis Saraiva Freitas6Rodrigo Almeida-Paes7Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-INI/Fiocruz, Rio de Janeiro 21040-360, BrazilLaboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-INI/Fiocruz, Rio de Janeiro 21040-360, BrazilLaboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-INI/Fiocruz, Rio de Janeiro 21040-360, BrazilLaboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21040-360, BrazilLaboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21040-360, BrazilLaboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-INI/Fiocruz, Rio de Janeiro 21040-360, BrazilLaboratório de Dermatologia Infecciosa, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-INI/Fiocruz, Rio de Janeiro 21040-900, BrazilLaboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-INI/Fiocruz, Rio de Janeiro 21040-360, BrazilSeveral human pathogenic fungi produce melanin. One of its properties during parasitism is the protection against antifungal drugs. This occurs with the agents of chromoblastomycosis, in which DHN-melanin reduces antifungal susceptibility to terbinafine and itraconazole. Since these agents are resistant to some antifungal drugs, we investigated the role of DHN-melanin on the <i>Fonsecaea</i> susceptibility to amphotericin B, micafungin, fluconazole, and flucytosine, drugs that usually present high minimal inhibitory concentrations (MIC) to this genus. Seven strains from three <i>Fonsecaea</i> human pathogenic species were treated with tricyclazole, a DHN-melanin inhibitor, and the MIC of the treated and untreated cells were compared. A survival assay was performed to confirm the alterations in the susceptibility of strains with reduced melanization, and the chitin levels of the strains were estimated by fluorescence. Tricyclazole did not affect fluconazole and flucytosine MIC, while melanin inhibition increased susceptibility to amphotericin B. Surprisingly, DHN-melanin inhibition decreased the susceptibility to micafungin. Survival assays confirmed this result on five strains. Cell wall chitin levels of the strains were not associated with the decrease in micafungin susceptibility. The results show that DHN-melanin does not have a role in the intrinsic resistance of <i>Fonseacaea</i> spp. to amphotericin B, fluconazole, and flucytosine, and its inhibition may promote micafungin resistance.https://www.mdpi.com/2036-7481/13/2/17antifungal susceptibilitychromoblastomycosis<i>Fonsecaea</i>DHN-melaninmicafungin |
| spellingShingle | Rowena Alves Coelho Maria Helena Galdino Figueiredo-Carvalho Juliana Vitória dos Santos Silva Dario Correa-Junior Susana Frases Rosely Maria Zancopé-Oliveira Dayvison Francis Saraiva Freitas Rodrigo Almeida-Paes Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The <i>Fonsecaea</i>/Micafungin Paradigm Microbiology Research antifungal susceptibility chromoblastomycosis <i>Fonsecaea</i> DHN-melanin micafungin |
| title | Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The <i>Fonsecaea</i>/Micafungin Paradigm |
| title_full | Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The <i>Fonsecaea</i>/Micafungin Paradigm |
| title_fullStr | Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The <i>Fonsecaea</i>/Micafungin Paradigm |
| title_full_unstemmed | Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The <i>Fonsecaea</i>/Micafungin Paradigm |
| title_short | Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The <i>Fonsecaea</i>/Micafungin Paradigm |
| title_sort | does dhn melanin always protect fungi against antifungal drugs the i fonsecaea i micafungin paradigm |
| topic | antifungal susceptibility chromoblastomycosis <i>Fonsecaea</i> DHN-melanin micafungin |
| url | https://www.mdpi.com/2036-7481/13/2/17 |
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