title: Tyrosine Detoxification Is an Essential Trait in the Life History of Blood-Feeding Arthropods.
abstract: Blood-feeding arthropods are vectors of infectious diseases such as dengue, Zika, Chagas disease, and malaria [1], and vector control is essential to limiting disease spread. Because these arthropods ingest very large amounts of blood, a protein-rich meal, huge amounts of amino acids are produced during digestion. Previous work on Rhodnius prolixus, a vector of Chagas disease, showed that, among all amino acids, only tyrosine degradation enzymes were overexpressed in the midgut compared to other tissues [2]. Here we demonstrate that tyrosine detoxification is an essential trait in the life history of blood-sucking arthropods. We found that silencing Rhodnius tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD), the first two enzymes of the phenylalanine/tyrosine degradation pathway, caused the death of insects after a blood meal. This was confirmed by using the HPPD inhibitor mesotrione, which selectively killed hematophagous arthropods but did not affect non-hematophagous insects. In addition, mosquitoes and kissing bugs died after feeding on mice that had previously received a therapeutic effective oral dose (1 mg/kg) of nitisinone, another HPPD inhibitor used in humans for the treatment of tyrosinemia type I [3]. These findings indicate that HPPD (and TAT) can be a target for the selective control of blood-sucking disease vector populations. Because HPPD inhibitors are extensively used as herbicides and in medicine, these compounds may provide an alternative less toxic to humans and more environmentally friendly than the conventional neurotoxic insecticides that are currently used, with the ability to affect only hematophagous arthropods.
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. Electronic address: msterkel29@gmail.com.
authors.forename: Marcos
authors.initials: M
authors.lastname: Sterkel
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
authors.forename: Hugo D
authors.initials: HD
authors.lastname: Perdomo
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
authors.forename: Melina G
authors.initials: MG
authors.lastname: Guizzo
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
authors.forename: Ana Beatriz F
authors.initials: AB
authors.lastname: Barletta
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
authors.forename: Rodrigo D
authors.initials: RD
authors.lastname: Nunes
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Dias
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular.
authors.forename: Marcos H F
authors.initials: MH
authors.lastname: Sorgine
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Electronic address: pedro@bioqmed.ufrj.br.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Oliveira
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D005260:Female; D020868:Gene Silencing; D008658:Inactivation, Metabolic; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009758:Nymph / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D012239:Rhodnius / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000235:genetics* / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D014443:Tyrosine; D015111:4-Hydroxyphenylpyruvate Dioxygenase; D014444:Tyrosine Transaminase
keywords: HPPD inhibitors; hematophagous vectors; neglected diseases; tyrosine metabolism