Supplementation with abscisic acid reduces malaria disease severity and parasite transmission

Elizabeth K K Glennon, L. Garry Adams, Derrick R. Hicks, Katayoon Dehesh, Shirley Luckhart

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1266-1275
Number of pages10
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume94
Issue number6
DOIs
StatePublished - Jun 1 2016

Fingerprint

Abscisic Acid
Malaria
Parasites
Culicidae
Parasitic Diseases
Parasitemia
Terpenes
Plasmodium falciparum
Infection
Eukaryota
Drug Resistance
Nitric Oxide Synthase
Meals
Mammals
Immunity
Nitric Oxide
Spleen
Eating
Pathology
Gene Expression

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases
  • Virology

Cite this

Supplementation with abscisic acid reduces malaria disease severity and parasite transmission. / Glennon, Elizabeth K K; Adams, L. Garry; Hicks, Derrick R.; Dehesh, Katayoon; Luckhart, Shirley.

In: American Journal of Tropical Medicine and Hygiene, Vol. 94, No. 6, 01.06.2016, p. 1266-1275.

Research output: Contribution to journalArticle

Glennon, Elizabeth K K ; Adams, L. Garry ; Hicks, Derrick R. ; Dehesh, Katayoon ; Luckhart, Shirley. / Supplementation with abscisic acid reduces malaria disease severity and parasite transmission. In: American Journal of Tropical Medicine and Hygiene. 2016 ; Vol. 94, No. 6. pp. 1266-1275.
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