Endophytic fungal compounds active against Cryptococcus neoformans and C. gattii

Area of Science:

• Mycology
• Natural Product Chemistry
• Medicinal Chemistry

Background:

• Cryptococcus infections are invasive fungal diseases causing severe illness and death, particularly in immunocompromised individuals.
• Increasing antifungal drug resistance in Cryptococcus necessitates the discovery of novel therapeutic agents.
• Endophytic fungi, residing within plant tissues, are a promising source of bioactive compounds.

Purpose of the Study:

• To investigate the antifungal potential of endophytic fungal extracts against Cryptococcus neoformans and Cryptococcus gattii.
• To isolate and characterize the active compounds responsible for the observed antifungal activity.
• To report novel antifungal compounds from the Mycosphaerella genus.

Main Methods:

• Screening of 400 ethanol extracts from endophytic fungi using microdilution broth assays.
• Bioassay-guided fractionation of the most active extract using liquid-liquid partitioning and semi-preparative HPLC.
• Determination of minimum inhibitory concentrations (MICs) for isolated compounds.

Main Results:

• An extract from Mycosphaerella sp. UFMGCB 2032 exhibited significant activity against both C. neoformans and C. gattii.
• Fractionation yielded two eicosanoic acids with potent antifungal properties: a novel compound (1) and myriocin (2).
• Compound 1 showed MICs of 1.3–2.50 μg/mL, and myriocin displayed MICs of 0.5 μg/mL against both fungal species.

Conclusions:

• Endophytic fungi, specifically Mycosphaerella sp., represent a valuable source of antifungal compounds.
• The identified eicosanoic acids, including myriocin, demonstrate potent activity against pathogenic Cryptococcus species.
• These findings suggest potential for developing new treatments for cryptococcosis, addressing the challenge of drug resistance.