Fungal Metabolite Asperaculane B Inhibits Malaria Infection and Transmission

Abstract

<jats:p>Mosquito-transmitted Plasmodium parasites cause millions of people worldwide to suffer malaria every year. Drug-resistant Plasmodium parasites and insecticide-resistant mosquitoes make malaria hard to control. Thus, the next generation of antimalarial drugs that inhibit malaria infection and transmission are needed. We screened our Global Fungal Extract Library (GFEL) and obtained a candidate that completely inhibited Plasmodium falciparum transmission to Anopheles gambiae. The candidate fungal strain was determined as Aspergillus aculeatus. The bioactive compound was purified and identified as asperaculane B. The concentration of 50% inhibition on P. falciparum transmission (IC50) is 7.89 µM. Notably, asperaculane B also inhibited the development of asexual P. falciparum with IC50 of 3 µM, and it is nontoxic to human cells. Therefore, asperaculane B is a new dual-functional antimalarial lead that has the potential to treat malaria and block malaria transmission.</jats:p>

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

“…Besides targeted by transmission-blocking vaccines, these interactive proteins can also be targeted by small molecules to block malaria transmission. The fungal secondary metabolite P -orlandin from Aspergillus niger ( Niu et al., 2015 ), asperaculane B from Aspergillus aculeatus ( Niu et al., 2020b ), and pulixin ( Niu et al., 2021 ) that prevent FREP1 in mosquito midgut from binding to sexual stage Plasmodium falciparum inhibit malaria transmission to mosquitoes. A synthetic polysulfonated polymer limits malaria transmission by inhibiting the interaction between midgut chondroitin sulfate glycosaminoglycans and ookinetes ( Mathias et al., 2013 ).…”

A diverse global fungal library for drug discovery

“…Notably, this is the first report about P. thomii and P. pancosmium that produce secondary metabolites with antimalarial activities. An independent project in our lab identified Asperaculane B as an active compound from this GFEL that inhibited malaria transmission to mosquitoes ( Niu et al, 2020 ).…”

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

“…About 10,000 fungal strains were isolated from these samples. The fungi were cultured on a large scale, as described previously in detail [ 23 ]. In short, the fungi were cultured with 500 g of Cheerios breakfast cereal (General Mills, Minneapolis, MN).…”