Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311

Area of Science:

• Natural Product Chemistry
• Microbiology
• Antimicrobial Discovery

Background:

• Fungus-growing ants rely on symbiotic bacteria for survival.
• Antimicrobial compounds produced by these symbionts can protect the ant colony.
• Streptomyces sp. ISID311 is a bacterial symbiont associated with Cyphomyrmex ants.

Purpose of the Study:

• To isolate and characterize antifungal macrolides from Streptomyces sp. ISID311.
• To evaluate the antimicrobial and antiprotozoal activities of the isolated compounds.
• To confirm the stereochemical assignments using bioinformatic analysis.

Main Methods:

• Isolation of compounds using chromatographic techniques.
• Structure elucidation via 1D and 2D NMR, MS analysis, and Kishi's method.
• Bioinformatic analysis of the cyphomycin biosynthetic gene cluster.
• Antifungal assays against Escovopsis sp. strains.
• Antiprotozoal assays against Leishmania donovani.

Main Results:

• Three antifungal macrolides, cyphomycin (1), caniferolide C (2), and GT-35 (3), were isolated.
• Structures and relative configurations were established using spectroscopic and bioinformatic methods.
• Compounds 1-3 demonstrated high antagonism against Escovopsis sp. fungi.
• Compounds 1-3 exhibited potent antiprotozoal activity against Leishmania donovani, with IC50 values as low as 0.073 µM.

Conclusions:

• Streptomyces sp. ISID311 produces novel antifungal macrolides with significant biological activities.
• These compounds represent potential leads for developing new antifungal and antiprotozoal agents.
• The study highlights the importance of exploring microbial symbionts for drug discovery.