A key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection.
Malaria infection renders humans more attractive toAnopheles gambiaesensu lato mosquitoes than uninfected people. The mechanisms remain unknown. We found that an isoprenoid precursor produced byPlasmodium falciparum, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), affectsA. gambiaes.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 aP. falciparum-infected blood meal, sporogony is increased.
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden.|Unit of Chemical Ecology, Department of Plant Protection Biology, SLU, SE 230 53 Alnarp, Sweden.
S Noushin
0000-0001-7239-4457
SN
Emami
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden.
Bo G
0000-0002-0892-9530
BG
Lindberg
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden.
Susanna
S
Hua
Unit of Chemical Ecology, Department of Plant Protection Biology, SLU, SE 230 53 Alnarp, Sweden.
Sharon R
0000-0002-6474-0214
SR
Hill
Department of Chemistry, Organic Chemistry, Royal Institute of Technology, SE 100 44 Stockholm, Sweden.|Laboratory of Chemical and Behavioral Ecology, Institute of Ecology, Nature Research Centre, LT-08412 Vilnius, Lithuania.
Raimondas
0000-0002-1719-2294
R
Mozuraitis
Department of Zoology, Stockholm University, SE 106 91 Stockholm, Sweden.
Philipp
0000-0001-8344-6830
P
Lehmann
Unit of Chemical Ecology, Department of Plant Protection Biology, SLU, SE 230 53 Alnarp, Sweden.
Göran
0000-0003-3063-893X
G
Birgersson
Department of Chemistry, Organic Chemistry, Royal Institute of Technology, SE 100 44 Stockholm, Sweden.
Anna-Karin
AK
Borg-Karlson
Unit of Chemical Ecology, Department of Plant Protection Biology, SLU, SE 230 53 Alnarp, Sweden.
Rickard
R
Ignell
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden. ingrid.faye@su.se.
Ingrid
0000-0003-4382-7238
I
Faye
D000818:Animals; D000852:Anopheles / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002245:Carbon Dioxide / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000469:parasitology; D000072138:Mosquito Vectors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009866:Oogenesis; D010755:Organophosphates / Q000378:metabolism* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000378:metabolism*; D013729:Terpenes / Q000378:metabolism; D014158:Transcription, Genetic; D014835:Volatilization
C467061:4-hydroxy-3-methyl-2-butenyl diphosphate; D010755:Organophosphates; D013729:Terpenes; D002245:Carbon Dioxide