Article
Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The Fonsecaea/Micafungin Paradigm
Registro en:
COELHO, Rowena Alves et al. Does DHN-Melanin Always Protect Fungi against Antifungal Drugs? The Fonsecaea/Micafungin Paradigm. Microbiology Research, v. 13, n. 2, p. 201-209, 2022.
2456-7043
10.3390/microbiolres13020017
2456-7043
Autor
Coelho, Rowena Alves
Figueiredo-Carvalho, Maria Helena Galdino
Silva, Juliana Vitória dos Santos
Correa-Junior, Dario
Frases, Susana
Zancopé-Oliveira, Rosely Maria
Freitas, Dayvison Francis Saraiva
Almeida-Paes, Rodrigo
Resumen
This research was funded by Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grant number E-26/201.441/2021 and Inova Fiocruz/VPPCB, grant number VPPCB-008-FIO-18-2-49. R.M.Z-O. was supported in part by Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq 302796/2017-7] and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro [FAPERJ E-26/202.527/2019]. 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 Fonsecaea susceptibility to amphotericin B, micafungin, fluconazole, and flucytosine, drugs that usually present high minimal inhibitory concentrations (MIC) to this genus. Seven strains from three Fonsecaea 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 Fonseacaea spp. to amphotericin B, fluconazole, and flucytosine, and its inhibition may promote micafungin resistance.