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

Malaria infection renders humans more attractive to sensu lato mosquitoes than uninfected people. The mechanisms remain unknown. We found that an isoprenoid precursor produced by , ()-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), affects 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 CO, 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 -infected blood meal, sporogony is increased.