A diverse global fungal library for drug discovery

Abstract

Background Secondary fungal metabolites are important sources for new drugs against infectious diseases and cancers. Methods To obtain a library with enough diversity, we collected about 2,395 soil samples and 2,324 plant samples from 36 regions in Africa, Asia, and North America. The collection areas covered various climate zones in the world. We examined the usability of the global fungal extract library (GFEL) against parasitic malaria transmission, Gram-positive and negative bacterial pathogens, and leukemia cells. Results Nearly ten thousand fungal strains were isolated. Sequences of nuclear ribosomal internal transcribed spacer (ITS) from 40 randomly selected strains showed that over 80% were unique. Screening GFEL, we found that the fungal extract from Penicillium thomii was able to block Plasmodium falciparum transmission to Anopheles gambiae, and the fungal extract from Tolypocladium album was able to kill myelogenous leukemia cell line K562. We also identified a set of candidate fungal extracts against bacterial pathogens.

Studies of the Parasite-Midgut Interaction Reveal Plasmodium Proteins Important for Malaria Transmission to Mosquitoes

“…To conduct antibody transmission-blocking assays, we suspended day 15-17 cultured P. falciparum with the fresh O+ type human blood to get the 0.2% final concentration of stage V gametocytes. Approximately 15 μL PBS containing 45 μg purified anti-Pfs16 rabbit polyclonal antibody was mixed with 285 μL infectious blood (final antibody concentration is 0.15 mg/ml), and an SMFA ( Niu et al., 2020a ) was conducted using 3-5 days old female naïve mosquitoes. After feeding for 30 m, the engorged mosquitoes were separated and maintained with 8% sugar in a BSL2 insectary (27°C, 12-h light/dark cycle, 80% humidity).…”

A novel fungal metabolite inhibits Plasmodium falciparum transmission and infection

“…Because FREP1–parasite interaction facilitates malaria transmission, we used an ELISA-based approach [ 18 ] to screen 1232 ethyl acetate extracts (40 µg/mL) in the global fungal extract library (GFEL) [ 20 ] that prevented FREP1 protein from binding to P. falciparum -infected cell lysate. The extracts that inhibited 90% of the FREP1 – parasite interaction were further analyzed for their activity in blocking malaria transmission with SMFA [ 18 ].…”

“…The discovery of the molecular mechanism of the FREP1–parasite interaction makes high-throughput screening of drugs against malaria transmission possible [ 12 ]. Targeting the mosquito FREP1-mediated Plasmodium transmission pathway, we screened fungal extracts from our newly established global fungal library [ 20 ] for inhibition of the FREP1– Plasmodium lysate interaction. Those extracts showing positive activity have the potential to inhibit malaria transmission.…”

“…Here we screened our global fungal library with more than 10,000 different fungal strains [ 20 ] and identified one novel compound that inhibited P. falciparum proliferation and transmission.…”

Discovery of mosquitocides from fungal extracts through a high-throughput cytotoxicity-screening approach

“…Our lab has recently established a large and diverse global fungal extract library (GFEL), which contains more than 10,000 fungal isolates and many more structurally diverse metabolites [ 21 ]. This library includes metabolites from some fungal species, e.g.…”