On the use of inhibitors of 4-hydroxyphenylpyruvate dioxygenase as a vector-selective insecticide in the control of mosquitoes

Ramírez, Marlon A. V.; Sterkel, Marcos; Martins, Ademir Jesús; Lima, José Bento Pereira; Oliveira, Pedro L.

doi:10.1101/669747

Cited by 2 publications

(3 citation statements)

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“…NTBC kills tsetse upon PLOS BIOLOGY cuticular application, and it can be safely administered to a mammalian host as an endectocide to kill Glossina upon bloodfeeding (and other hematophagous arthropods feeding on the treated mammal [11]). In agreement with our results on tsetse, a recent preprint article from the Oliveira's group has shown evidence that NTBC is more potent than mesotrione and isoxaflutole against Aedes aegypti mosquitoes [33]. Moreover, NTBC was also found to be lethal against Anopheles and Culex as well as Ae.…”

Section: Discussionsupporting

confidence: 92%

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Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

et al. 2021

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Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populations of insect pollinator species. Here we present a promising, environment-friendly alternative to current insecticides that targets the insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded and eliminated. RNA interference (RNAi) of either the first two enzymes in the tyrosine degradation pathway (tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, oral administration of NTBC to bumblebees did not affect their survival. Using a novel mathematical model, we show that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current disease elimination programmes.

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Section: Discussionsupporting

confidence: 92%

“…Moreover, NTBC was also found to be lethal against Anopheles and Culex as well as Ae . aegypti strains resistant to neurotoxic insecticides [ 33 ], indicating that cross-resistance between these compounds and NTBC is unlikely.…”

Section: Discussionmentioning

confidence: 99%

Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

et al. 2021

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“…The different feeding habits can shape the function of genes; the loss of function of these genes could have different, sometimes opposite, effects in related species with different diets. For example, inhibition of the tyrosine catabolism pathway extends the lifespan of D. melanogaster (Parkhitko et al, 2020) and Caenorhabditis elegans (Ferguson et al, 2013; Lee et al, 2003) but causes hematophagous arthropods death after a blood meal due to tyrosine accumulation and precipitation (Ramirez et al, 2021; Sterkel et al, 2021, 2016; Sterkel and Oliveira, 2017). Here we demonstrated that the silencing of the eIF3m gene, different from the phenotypes described in D. melanogaster that were only mild and tissue-specific (D’Brot et al, 2013; Kang et al, 2017), drastically affected R. prolixus physiology, causing a delay in blood meal digestion that affected moulting, reproduction and survival.…”

Section: Discussionmentioning

confidence: 99%

eIF3 subunit M regulates blood meal digestion in Rhodnius prolixus affecting ecdysis, reproduction and survival

Ameijeiras

Capriotti

Ons

et al. 2022

Preprint

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In triatomines, blood-feeding triggers many physiological processes, including post-embryonic development and reproduction. Different feeding habits, such as hematophagy, can shape gene functions to meet the challenges of each type of diet. A comparison of transcriptomic and proteomic data indicates that post-transcriptional regulation of gene expression is crucial in triatomines, so we evaluated the impact of RNAi silencing of the eukaryotic translation initiation factors 3 subunit m (eIF3m) in R. prolixus physiology. We showed that eIF3m is essential for correct digestion, affecting the processes triggered by a blood meal. The silencing of this gene inhibited moulting and caused the premature death of nymphs, while in adult females inhibited oviposition and increased resistance to starvation. Male survival was not affected by eIF3m knockdown. The information regarding the eIF3m function in insects is scarce. The phenotypes observed in R. prolixus upon eIF3m gene silencing are different and more severe than those described in Drosophila melanogaster, pointing to the particular importance of this gene in triatomines.

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On the use of inhibitors of 4-hydroxyphenylpyruvate dioxygenase as a vector-selective insecticide in the control of mosquitoes

Cited by 2 publications

References 57 publications

Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

eIF3 subunit M regulates blood meal digestion in Rhodnius prolixus affecting ecdysis, reproduction and survival

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