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

Marlon A Vergaray Ramirez,Ademir J Martins,José Bp Lima,Pedro L Oliveira,Marcos Sterkel

doi:10.1002/ps.6679

Abstract

Blood-sucking insects incorporate many times their body weight of blood in a single meal. Because proteins are the major component of vertebrate blood, its digestion in the gut generates extremely high concentrations of free amino acids. Previous reports showed that the tyrosine degradation pathway plays an essential role in adapting these animals to blood feeding. Inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD), the rate-limiting step of tyrosine degradation, results in the death of insects after a blood meal. Therefore, it has been suggested that compounds that block the catabolism of tyrosine could act selectively on blood-feeding insects. Here, we evaluated the toxicity against mosquitoes of three HPPD inhibitors currently used as herbicides and in human health. Of the compounds tested, nitisinone (NTBC) proved to be more potent than mesotrione (MES) and isoxaflutole (IFT) in Aedes aegypti. NTBC was lethal to Ae. aegypti in artificial feeding assays [median lethal dose (LD50 ): 4.53 μm] and in topical application (LD50 : 0.012 nmol/mosquito). NTBC was also lethal to Ae. aegypti populations that were resistant to neurotoxic insecticides, and to other mosquito species (Anopheles and Culex). HPPD inhibitors, particularly NTBC, represent promising new drugs for mosquito control. Because they affect only blood-feeding organisms, they represent a safer and more environmentally friendly alternative to conventional neurotoxic insecticides. © 2021 Society of Chemical Industry.

Highlights

Mosquitoes are important vectors for pathogens that cause diseases such as malaria, lymphatic filariasis, yellow fever, dengue, chikungunya, Zika and West Nile fever
The control of mosquitoes has been pursued in the last decades by the use of neurotoxic insecticides to prevent the spreading of dengue, zika and malaria, among other diseases
Results showed that Nitisinone (NTBC), an inhibitor used in medicine, was the most potent of them

Summary

Introduction

Mosquitoes are important vectors for pathogens that cause diseases such as malaria, lymphatic filariasis, yellow fever, dengue, chikungunya, Zika and West Nile fever. The main classes of insecticides are organochlorines, organophosphates, carbamates, and pyrethroids, all of them neurotoxic [6] Their extensive use has led to the development of resistance to these insecticides [7,8], representing a problem for mosquito control. This is true for arbovirus transmitted by Ae. aegypti, exemplified by the recent global Zika outbreak [9], making the search for alternative methods for mosquito control a high priority of the global public health agenda [10]

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