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A natural agonist of mosquito TRPA1 from the medicinal plant Cinnamosma fragrans that is toxic, antifeedant, and repellent to the yellow fever mosquito Aedes aegypti.

ABSTRACT: Plants produce various secondary metabolites that offer a potential source of novel insecticides and repellents for the control of mosquito vectors. Plants of the genus Cinnamosma are endemic to, and widely-distributed throughout, the island of Madagascar. The barks of these species are commonly used in traditional medicines for treating a wide range of maladies. The therapeutic nature of the bark is thought to be associated with its enrichment of pungent drimane sesquiterpenes, which elicit antifeedant and toxic effects in some insects. Here we test the hypothesis that a bark extract of Cinnamosma fragrans (CINEX) and its major drimane sesquiterpenes are insecticidal, antifeedant, and repellent to Aedes aegypti, the principal mosquito vector of chikungunya, dengue, yellow fever, and Zika viruses. We demonstrate that CINEX is 1) toxic to larval and adult female mosquitoes, and 2) antifeedant and repellent to adult female mosquitoes. Moreover, we show that cinnamodial (CDIAL), a sesquiterpene dialdehyde isolated from CINEX, duplicates these bioactivities and exhibits similar toxic potency against pyrethroid-susceptible and -resistant strains of Ae. aegypti. Importantly, we show that CDIAL is an agonist of heterologously-expressed mosquito Transient Receptor Potential A1 (TRPA1) channels, and the antifeedant activity of CDIAL is dampened in a TRPA1-deficient strain of Ae. aegypti (TRPA1-/-). Intriguingly, TRPA1-/- mosquitoes do not exhibit toxic resistance to CDIAL. The data indicate that modulation of TRPA1 is required for the sensory detection and avoidance of CDIAL by mosquitoes, but not for inducing the molecule's toxicity. Our study suggests that CDIAL may serve as a novel chemical platform for the development of natural product-based insecticides and repellents for controlling mosquito vectors.

SUBMITTER: Inocente EA

PROVIDER: S-EPMC5823474 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

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A natural agonist of mosquito TRPA1 from the medicinal plant Cinnamosma fragrans that is toxic, antifeedant, and repellent to the yellow fever mosquito Aedes aegypti.

Inocente Edna Alfaro EA Shaya Marguerite M Acosta Nuris N Rakotondraibe L Harinantenaina LH Piermarini Peter M PM

PLoS neglected tropical diseases 20180209 2

Plants produce various secondary metabolites that offer a potential source of novel insecticides and repellents for the control of mosquito vectors. Plants of the genus Cinnamosma are endemic to, and widely-distributed throughout, the island of Madagascar. The barks of these species are commonly used in traditional medicines for treating a wide range of maladies. The therapeutic nature of the bark is thought to be associated with its enrichment of pungent drimane sesquiterpenes, which elicit ant ...[more]

PMID: 29425195

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Project description:BackgroundMosquitoes are important pathogen vectors affecting human and other animals. Studies on genetic control of mosquito mediated disease transmission gained traction recently due to mosquito transgenesis technology. Active transposons are considered valuable tools to propagate pathogen resistance transgenes among mosquitoes, rendering the whole population recalcitrant to diseases. A major hurdle in this approach is the inefficient remobilization activity after the integration of heterologous transposon vectors bearing transgenes into chromosomes. Therefore, endogenous active transposons in mosquito genomes are highly desirable.ResultsStarting with the transposable element database of the yellow fever mosquito Aedes aegypti genome, detailed analyses of the members of each TE family were performed to identify sequences with multiple identical copies, an indicator of their latest or current transposition activity. Among a dozen of potentially active TE families, two DNA elements (TF000728 and TF000742 in TEfam) are short and nonautonomous. Close inspection of the elements revealed that these two families were previously mis-categorized and, unlike other known TEs, insert specifically at dinucleotide "AT". These two families were therefore designated as ATon-I and ATon-II. ATon-I has a total copy number of 294, among which three elements have more than 10 identical copies (146, 61 and 17). ATon-II has a total copy number of 317, among which three elements have more than 10 identical copies (84, 15 and 12). Genome wide searches revealed additional 24 ATon families in A. aegypti genome with nearly 6500 copies in total. Transposon display analysis of ATon-1 family using different A. aegypti strains suggests that the elements are similarly abundant in the tested mosquito strains.ConclusionATons are novel mobile genetic elements bearing terminal inverted repeats and insert specifically at dinucleotide "AT". Five ATon families contain elements existing at more than 10 identical copies, suggesting very recent or current transposition activity. A total of 24 new TE families with nearly 6000 copies were identified in this study.

Dataset Information

A natural agonist of mosquito TRPA1 from the medicinal plant Cinnamosma fragrans that is toxic, antifeedant, and repellent to the yellow fever mosquito Aedes aegypti.

Publications

A natural agonist of mosquito TRPA1 from the medicinal plant Cinnamosma fragrans that is toxic, antifeedant, and repellent to the yellow fever mosquito Aedes aegypti.

Similar Datasets

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