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A Novel Fungal Metabolite Inhibits Plasmodium falciparum Transmission and Infection

Summary

Scientists have discovered a new compound from a soil fungus that could help fight malaria in two important ways. This compound, called pulixin, not only prevents malaria parasites from infecting mosquitoes (stopping disease spread) but also kills the parasites in blood cells (treating the disease). This is particularly exciting because it works differently from existing malaria drugs and could help address the growing problem of drug resistance. Impacts on everyday life: • Could lead to new malaria treatments that work better than current drugs • May help reduce malaria transmission in communities through novel spray applications • Demonstrates the potential of natural compounds from fungi as sources of new medicines • Could help combat the growing problem of drug-resistant malaria • May provide a safer alternative to current antimalarial drugs with fewer side effects

Background

Malaria transmission depends on infected mosquitoes and can be controlled by transmission-blocking drugs. The recently discovered FREP1-mediated malaria transmission pathway presents an excellent target for screening drugs to limit transmission. Plasmodium parasites transmitted by anopheline mosquitoes caused approximately 200 million clinical malaria cases and half a million deaths in 2019. While most antimalarial drugs kill parasites at the blood stage, the spread of insecticide resistance in mosquito populations and lack of vaccines has prompted the need for new malaria control strategies.

Objective

To identify and characterize novel small molecules from fungal sources that can interrupt malaria transmission by targeting the FREP1-Plasmodium interaction pathway.

Results

The researchers identified an extract from the fungus Purpureocillium lilacinum that completely inhibited P. falciparum transmission at 1 μg/mL. From this extract, they isolated and characterized a novel compound named pulixin (3-amino-7,9-dihydroxy-1-methyl-6H-benzo[c]chromen-6-one). Pulixin blocked malaria transmission with an EC50 of 11 μM and inhibited asexual P. falciparum development with an EC50 of 47 nM. The compound showed no significant cytotoxicity to human cells at concentrations up to 116 μM.

Conclusion

The researchers discovered a novel natural compound, pulixin, from Purpureocillium lilacinum that effectively blocks both malaria transmission and parasite replication. The compound works by targeting the FREP1-mediated transmission pathway and shows promise as a new tool for malaria control with dual therapeutic action against both transmission and blood-stage infection.
  • Published in:Parasites & Vectors,
  • Study Type:Laboratory Research,
  • Source: 10.1186/s13071-021-04677-7
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