Natural products involved in the symbiosis between Streptomyces spp. and social insects

Author(s)

Carla Menegatti

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2021-02-22

Examining board members

Monica Tallarico Pupo; Warley de Souza Borges; Taícia Pacheco Fill; Lívia Soman de Medeiros

• Advisor: Monica Tallarico Pupo

Abstract

Microbial natural products play an important role in the discovery of new bioactive compounds. Insects and microorganisms are involved in complex symbiotic interactions and many novel and bioactive natural compounds have been identified in these relationships. Social insects are subjected to climatic and population conditions that increase their susceptibility to parasites. Thus, one of the defense strategies acquired during the evolution of insects was the symbiotic association with bacteria capable of biosynthesizing antimicrobial compounds against pathogens. This work studied the natural products biosynthesized by bacteria associated with leaf-cutter ants Acromyrmex ap. and the stingless bee Melipona scutellaris. Biological screenings against entomopathogens led to the selection of four actinobacteria associated with ants, active against the fungus Escovopsis, and another strain associated with bees, active against the bacteria Paenibacillus larvae, to be chemically studied using chromatographic, spectroscopic, and spectrometric methods. The extracts were prepared and tested against the parasites Trypanosoma cruzi, Leishmania donovani and L. infantum. The actinobacterium Streptomyces sp. ICBG 328 inhibited two Escovopsis strains and its ethyl acetate extract displayed good inhibition against the parasites T. cruzi and L. donovani. Six analogous polyketides known as chromomycins (22, 23, 24, 25, 26 and 27) were isolated from the ethyl acetate extract of Streptomyces sp. ICBG 328, and three of them showed high leishmanicidal activity. The actinobacterium Streptomyces sp. ICBG 197 was active against five Escovopsis strains and its acetone extract showed 94% inhibition against the parasite L. donovani. Nystatin was isolated from its extract (28) and showed antifungal activity against two Escovopsis strains, suggesting a possible defensive role of Streptomyces ICBG 197 in the ecological association with Acromyrmex ants. Streptomyces sp. ICBG 171 also showed activity against parasites, and the compounds nigericin (29), elaiophylin (30), 11-O-methylelaiophylin (31) and 11,11-O, O-dimethyllelaiophylin (32) were isolated from its acetone extract. Compound 29 is active against the fungus Escovopsis and 29, 30, 31 and 32 are known for their high antiparasitic activity. The actinobacteria Streptomyces ICBG1318 was isolated from the stingless bee Melipona scutellaris and produced two novel cyclodepsipeptides, named as meliponamycin A (33) and meliponamycin B (34), which were highly active against the entomopathogen P. larvae and showed activity against the human pathogens S. aureus and L. infantum. Thus, this work reports the isolation and identification of several compounds possibly involved in the mediation of symbiotic interactions between bacteria and social insects, as well as their leishmanicidal potential. The actinobacteria Streptomyces sp. ICBG 1318 may positively impact M. scutellaris natural environment by the ability of biosynthesize novel and bioactive meliponamycins. (AU)

• FAPESP's process: 16/15576-3 - Natural products involved in symbiosis between actinobacteria and social insects
• Grantee: Carla Menegatti
• Support Opportunities: Scholarships in Brazil - Doctorate