Antifungal compounds from Streptomyces associated with attine ants also inhibit Leishmania donovani

Abstract

Bacterial strains isolated from attine ants showed activity against the insect specialized fungal pathogen Escovopsis and also against the human protozoan parasite Leishmania donovani . The bioassay guided fractionation of extracts from cultures of Streptomyces sp. ICBG292, isolated from the exoskeleton of Cyphomyrmex workers, led to the isolation of Mer-A2026B ( 1 ), piericidin-A 1 ( 2 ) and nigericin ( 3 ). Nigericin ( 3 ) presented high activity against intracellular amastigotes of L . donovani (IC 50 0.129 ± 0.008 μM). Streptomyces puniceus ICBG378, isolated from workers of Acromyrmex rugosus rugosus , produced dinactin ( 4 ) with potent anti- L . donovani activity against intracellular amastigotes (IC 50 0.018 ± 0.003 μM). Compounds 3 and 4 showed good selectivity indexes, 88.91 and 656.11 respectively, and were more active than positive control, miltefosine. Compounds 1 – 4 were also active against some Escovopsis strains. Compounds 1 and 2 were also produced by Streptomyces sp. ICBG233, isolated from workers of Atta sexdens , and detected in ants’ extracts by mass spectrometry, suggesting they are produced in the natural environment as defensive compounds involved in the symbiotic interaction.

Chemical Ecology in Insect-microbe Interactions in the Neotropics

“…The actinobacterium S. puniceus ICBG378, isolated from Acromyrmex rugosus rugosus ants, produces griseorhodin A (12) and griseorhodin C (13), natural products known by their cytotoxic activity against cancer cell lines [46], and dinactin (14), active against Escovopsis (▶ Fig. 2) [47]. Dinactin (14) was also active against Leishmania donovani, one of the etiological agents of leishmaniasis, a neglected tropical disease that causes thousands of deaths yearly in developing countries.…”

“…2), all active against Escovopsis and against intracellular amastigotes of L. donovani. Compounds 15 and 16 were also isolated from Atta-associated Streptomyces, while 14 and 17 showed the most potent leishmanicidal activities, with good selectivity indexes [47]. The biological activity of these compounds highlights the importance of exploring different sources for prospecting compounds that can help treating human diseases [47].…”

“…Compounds 15 and 16 were also isolated from Atta-associated Streptomyces, while 14 and 17 showed the most potent leishmanicidal activities, with good selectivity indexes [47]. The biological activity of these compounds highlights the importance of exploring different sources for prospecting compounds that can help treating human diseases [47]. The hypothesis that the ant microbiome is a good source for exploring new medically useful antimicrobial agents was further reiterated.…”

Chemical warfare between fungus-growing ants and their pathogens

“… Antileishmanial activity. [ 41 ] Av25_2 A. volcanus Actinomycin D ( 16 ) Actinomycin X2 ( 17 ) Active against Pseudonocardia and Streptomyces spp . [ 39 ] Pseudonocardia CC011120-4 Apterostigma dentigerum Dentigerumycin A ( 6 ) Antifungal activity against E. weberi [ 32 ] P. octospinosus P1 A. octospinosus Nystatin P1 ( 7 ) Antifungal activity against E. weberi [ 29 , 36 ] HH130629-09, HH130630-07 Apterostigma sp.…”

Compostos carbonílicos α,β-insaturados e hidrazonas sintéticas como antiparasitários

“…Logo, foi necessário que todos os compostos após recristalização fossem submetidos a bomba de alto vácuo por um período mínimo de 24 horas para garantir a total remoção do ácido acético.Os ensaios contra parasita do gênero Leishmania, foram realizados contra as formas promastigotas, o estágio infectante e amastigotas, as formas intracelulares do parasita.Considera-se as formas amastigotas clinicamente mais relevantes, visto que se reproduzem no macrófago, podendo romper a célula e infectar as células dos arredores. Todavia, a obtenção da atividade frente as duas formas do parasita nos dispõem de informações importantes para poder guiar-nos a elucidar os mecanismos de ação dos compostos avaliados(ORTEGA et al, 2019). apresentaram valores de IC50 inferiores a 20 µM.…”