Metabolomic profiling of permethrin-treated Drosophila melanogaster identifies a role for tryptophan catabolism in insecticide survival

Abstract

Insecticides and associated synergists are rapidly losing efficacy in target insect pest populations making the discovery of alternatives a priority. To discover novel targets for permethrin synergists, metabolomics was performed on permethrin-treated Drosophila melanogaster. Changes were observed in several metabolic pathways including those for amino acids, glycogen, glycolysis, energy, nitrogen, NAD + , purine, pyrimidine, lipids and carnitine.Markers for acidosis, ammonia stress, oxidative stress and detoxification responses were also observed. Many of these changes had not been previously characterized after permethrin exposure. From the altered pathways, tryptophan catabolism was selected for further investigation. The knockdown of some tryptophan catabolism genes (vermilion, cinnabar and CG6950) in the whole fly and in specific tissues including fat body, midgut and Malpighian tubules using targeted RNAi resulted in altered survival phenotypes against acute topical permethrin exposure. The knockdown of vermilion, cinnabar and CG6950 in the whole fly also altered survival phenotypes against chronic oral permethrin, fenvalerate, DDT, chlorpyriphos and hydramethylnon exposure. Thus tryptophan catabolism has a previously uncharacterized role in defence against insecticides, and shows that metabolomics is a powerful tool for target identification in pesticide research.

Vgsc-interacting proteins are genetically associated with pyrethroid resistance in Aedes aegypti

“…Over-representation of the metabolic gene category is consistent with studies in drosophilids wherein amino acid catabolism was tied to permethrin sensitivity [57]. Specifically, Brinzer et al found a decrease in proline levels in resistant larvae that had been exposed to permethrin, which could be explained by either increased conversion from proline to glutamate or inhibition of the proline precursor ornithine.…”

“…Conversion of proline to glutamate has also been reported upon exposure to malathion or DDT [58,59]. In the current work, the aedine ortholog of 5-oxoprolinase, responsible for the degradation of glutamate, which would be required if it was in excess, is present in the high association group (S2 Table) [57].…”

Inhibiting the proteasome reduces molecular and biological impacts of the natural product insecticide, spinosad

“…In general, our understanding of what transpires downstream of the interaction between an insecticide and its target is fragmented; SPIN is not an isolated case. There is accumulating evidence of low‐dose insecticide exposures causing significant perturbations of metabolism and energy production 2, 48 . Given current concerns about the potential for sub‐lethal doses of insecticides to threaten the viability of non‐pest insect populations, 49‐51 there is a need to fill the gap in our understanding of what transpires between the insecticide–target interaction and the behavioural and fitness defects being investigated so intensively.…”

Metabolomics‐on‐a‐chip approach to study hepatotoxicity of DDT, permethrin and their mixtures

“…In other words, metabolomics can be used to identify the potential biomarkers of toxicity. In last years, some metabolomics studies of the impact of PMT (Brinzer et al, ; Li, Wang, Lu, Wei, & Kong, ; Liang, Wang, Long, & Wu, ) and DDT (McKelvie, Yuk, Xu, Simpson, & Simpson, ; Song, Chen, et al, ; Song, Zheng, et al, ; Zuluaga, Melchor, Tabares‐Villa, Taborda, & Sepulveda‐Arias, ) on metabolism have been reported in the literature. Metabolomics studies of pesticide exposures are most often realized from organ extracts, blood, urine and plasma.…”