title: Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission.
abstract: Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California.
authors.forename: Elizabeth K K
authors.initials: EK
authors.lastname: Glennon
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California.
authors.forename: L Garry
authors.initials: LG
authors.lastname: Adams
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California.
authors.forename: Derrick R
authors.initials: DR
authors.lastname: Hicks
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California.
authors.forename: Katayoon
authors.initials: K
authors.lastname: Dehesh
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California sluckhart@ucdavis.edu.
authors.forename: Shirley
authors.initials: S
authors.lastname: Luckhart
mesh_terms: D000040:Abscisic Acid / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000962:Antimalarials / Q000627:therapeutic use*; D019587:Dietary Supplements; D005260:Female; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D010967:Plasmodium yoelii
chemical_list: D000962:Antimalarials; D000040:Abscisic Acid