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

Abstract

Malaria infection renders humans more attractive to <i>Anopheles gambiae</i> sensu lato mosquitoes than uninfected people. The mechanisms remain unknown. We found that an isoprenoid precursor produced by <i>Plasmodium falciparum</i>, (<i>E</i>)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), affects <i>A. gambiae</i> 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 <i>P. falciparum</i>-infected blood meal, sporogony is increased.