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

Author(s)

Ortega, Humberto E. ^[1] ; Ferreira, Leonardo L. G. ^[2] ; Melo, Weilan G. P. ^[1] ; Oliveira, Ana Ligia L. ^{[3, 1]} ; Ramos Alvarenga, Rene F. ^[4] ; Lopes, Norberto P. ^[1] ; Bugni, Tim S. ^[4] ; Andricopulo, Adriano D. ^[2] ; Pupo, Monica T. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Lab Quim Med & Computac, Ctr Pesquisa & Inovacao Biodiversidade & Farmacos, Sao Carlos, SP - Brazil

^[3] Univ Fed Amazonas, Fac Ciencias Farmaceut, Manaus, Amazonas - Brazil

^[4] Univ Wisconsin Madison, Div Pharmaceut Sci, Madison, WI - USA

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 13, n. 8 AUG 2019.
• Web of Science Citations: 0

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 (IC50 0.129 +/- 0.008 mu M). Streptomyces puniceus ICBG378, isolated from workers of Acromyrmex rugosus rugosus, produced dinactin (4) with potent anti-L. donovani activity against intracellular amastigotes (IC50 0.018 +/- 0.003 mu M). 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. (AU)

• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/50954-0 - Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates
• Grantee: Mônica Tallarico Pupo
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 15/01001-6 - Discovering bacterial symbionts diversity associated with ants in different Brazilian biomes
• Grantee: Weilan Gomes da Paixão Melo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/14095-6 - Bacterial symbionts isolated from fungus-growing ants collected in remaining hotspots of biodiversity in São Paulo State as sources of antiparasitic compounds
• Grantee: Humberto Enrique Ortega Dominguez
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 16/15872-1 - Identification of natural antiparasitic products produced by insect–bacterial symbiosis
• Grantee: Ana Lígia Leandrini de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/20154-0 - Exploring antimicrobial, anticancer and antiparasitic compounds from bacterial symbionts isolated from Acromyrmex ants, collected in São Paulo State, Brazil
• Grantee: Humberto Enrique Ortega Dominguez
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)