Understanding pathogen-insect interaction to block vector-borne diseases

Image

Dr. Jun Li's project summary:

Mosquitoes transmit many diseases including Zika and malaria. Malaria alone is responsible for about two hundred million clinical cases worldwide and kills nearly one million a year. Malaria is caused by Plasmodium parasites and transmitted by anopheline mosquitoes. Zika can trigger paralysis and birth defects. Inhibiting pathogen development in mosquitoes will block disease transmission. Dr. Jun Li's research aims to find target genes that are essential for pathogen transmission in mosquitoes. Moreover, Dr. Li develops drugs targeting these critical genes to stop disease transmission.

By genomic approaches, Li's research laboratory discovered that fibrinogen-related protein 1 (FREP1) is critical for malaria parasite infection in Anopheles gambiae and it facilitates Plasmodium invasion in mosquitoes through interacting with gametocytes and ookinetes. Furthermore, they tested the hypothesis that small molecules disrupting this interaction will prevent parasites from infecting mosquitoes. Li's research team screened a fungal extract library and obtained a candidate fungal extract of Aspergillus niger that specifically inhibited the interaction between FREP1 and P. falciparum infected erythrocytes by about 92%. Notably, feeding mosquitoes with the candidate fungal extract significantly inhibited P. falciparum infection in the mosquito midgut. A bioactive non-cytotoxic compound that prevents FREP1 from binding to gametocytes or ookinetes was isolated and identified as P-orlandin. Importantly, P-orlandin significantly reduced P. falciparum infection intensity in mosquitoes.

In summary, Dr. Li discovered FREP1 as a key gene to mediate malaria transmission. Disruption of the interaction between FREP1 and parasites effectively reduces Plasmodium infection in mosquitoes. Targeting FREP1 and other key mosquito molecules that are responsible for pathogen invasion with small molecules is thus an effective novel approach to block the transmission of mosquito-transmitted diseases.