In vitro activity of the anthelmintic drug niclosamide against Sporothrix spp. strains with distinct genetic and antifungal susceptibility backgrounds.
Sporothrix brasiliensis
Drug repurposing
Niclosamide
Sporotrichosis
Journal
Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]
ISSN: 1678-4405
Titre abrégé: Braz J Microbiol
Pays: Brazil
ID NLM: 101095924
Informations de publication
Date de publication:
11 Mar 2024
11 Mar 2024
Historique:
received:
31
10
2023
accepted:
07
03
2024
medline:
11
3
2024
pubmed:
11
3
2024
entrez:
11
3
2024
Statut:
aheadofprint
Résumé
The drugs available to treat sporotrichosis, an important yet neglected fungal infection, are limited. Some Sporothrix spp. strains present reduced susceptibility to these antifungals. Furthermore, some patients may not be indicated to use these drugs, while others may not respond to the therapy. The anthelmintic drug niclosamide is fungicidal against the Sporothrix brasiliensis type strain. This study aimed to evaluate whether niclosamide also has antifungal activity against Sporothrix globosa, Sporothrix schenckii and other S. brasiliensis strains with distinct genotypes and antifungal susceptibility status. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined using the microdilution method according to the CLSI protocol. The checkerboard method was employed to evaluate niclosamide synergism with drugs used in sporotrichosis treatment. Metabolic activity of the strains under niclosamide treatment was evaluated using the resazurin dye. Niclosamide was active against all S. brasiliensis strains (n = 17), but it was ineffective (MIC > 20 µM) for some strains (n = 4) of other pathogenic Sporothrix species. Niclosamide MIC values for Sporothrix spp. were similar for mycelial and yeast-like forms of the strains (P = 0.6604). Niclosamide was fungicidal (MFC/MIC ratio ≤ 2) for most strains studied (89%). Niclosamide activity against S. brasiliensis is independent of the fungal genotype or non-wild-type phenotypes for amphotericin B, itraconazole, or terbinafine. These antifungal drugs presented indifferent interactions with niclosamide. Niclosamide has demonstrated potential for repurposing as a treatment for sporotrichosis, particularly in S. brasiliensis cases, instigating in vivo studies to validate the in vitro findings.
Identifiants
pubmed: 38466550
doi: 10.1007/s42770-024-01301-5
pii: 10.1007/s42770-024-01301-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
ID : E-26/201.441/2021
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 405653/2021-2
Organisme : Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
ID : 23/2551-0000503-4
Organisme : INI/Fiocruz
ID : INI-003-FIO-19-2-7
Organisme : Programa Inova Fiocruz
ID : PRES-008-FIO-22-2-11
Informations de copyright
© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.
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