Venturicidin A affects the mitochondrial membrane potential and induces kDNA loss in Trypanosoma brucei.
Antimicrob Agents Chemother
; 68(7): e0167123, 2024 Jul 09.
Article
em En
| MEDLINE
| ID: mdl-38869301
ABSTRACT
Neglected tropical diseases caused by trypanosomatid parasites have devastating health and economic consequences, especially in tropical areas. New drugs or new combination therapies to fight these parasites are urgently needed. Venturicidin A, a macrolide extracted from Streptomyces, inhibits the ATP synthase complex of fungi and bacteria. However, its effect on trypanosomatids is not fully understood. In this study, we tested venturicidin A on a panel of trypanosomatid parasites using Alamar Blue assays and found it to be highly active against Trypanosoma brucei and Leishmania donovani, but much less so against Trypanosoma evansi. Using fluorescence microscopy, we observed a rapid loss of the mitochondrial membrane potential in T. brucei bloodstream forms upon venturicidin A treatment. Additionally, we report the loss of mitochondrial DNA in approximately 40%-50% of the treated parasites. We conclude that venturicidin A targets the ATP synthase of T. brucei, and we suggest that this macrolide could be a candidate for anti-trypanosomatid drug repurposing, drug combinations, or medicinal chemistry programs.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trypanosoma brucei brucei
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DNA de Cinetoplasto
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Macrolídeos
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Potencial da Membrana Mitocondrial
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article