Venturicidin A affects the mitochondrial membrane potential and induces kDNA loss in Trypanosoma brucei.
Antimicrob Agents Chemother
; 68(7): e0167123, 2024 Jul 09.
Article
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trypanosoma brucei brucei
/
ADN de Cinetoplasto
/
Macrólidos
/
Potencial de la Membrana Mitocondrial
Límite:
Animals
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
Estados Unidos