A key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection

Siren molecule calls loudly to mosquitoes People infected by malaria become more attractive to the mosquito vectors of the disease, which facilitates the spread of malaria. Emami et al. found that red blood cells of the host respond to a parasite-derived isoprenoid called HMBPP by increasing the production of carbon dioxide and several monoterpenes and aldehydes. Mosquitoes fed HMBPP-spiked blood displayed malaria parasite–specific changes in gene transcription, which reinforced attractiveness for the mosquito. HMBPP also stimulates mosquito feeding and malaria parasite reproduction. Thus, the parasite manipulates its mammalian host to make it more attractive to the insect vectors and exploits the same molecule to amplify transmission. Science, this issue p. 1076 An isoprenoid released by Plasmodium-infected red blood cells has several functions in enhancing parasite transmission. Malaria infection renders humans more attractive to Anopheles gambiae sensu lato mosquitoes than uninfected people. The mechanisms remain unknown. We found that an isoprenoid precursor produced by Plasmodium falciparum, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), affects A. gambiae s.l. blood meal seeking and feeding behaviors as well as susceptibility to infection. HMBPP acts indirectly by triggering human red blood cells to increase the release of CO2, aldehydes, and monoterpenes, which together enhance vector attraction and stimulate vector feeding. When offered in a blood meal, HMBPP modulates neural, antimalarial, and oogenic gene transcription without affecting mosquito survival or fecundity; in a P. falciparum–infected blood meal, sporogony is increased.

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