Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis
- Autores
- Sterkel, Marcos; Haines, Lee R.; Casas Sánchez, Aitor; Adung'a, Vincent Owino; Vionette Amaral, Raquel J.; Quek, Shannon; Rose, Clair; dos Santos, Mariana Silva; Escude, Natalia García; Ismail, Hanafy M.; Paine, Mark I.; Barribeau, Seth M.; Wagstaff, Simon; MacRae, James I.; Masiga, Daniel; Yakob, Laith; Oliveira, Pedro L.; Acosta Serrano, Álvaro
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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-hydroxyphe-nylpyruvate 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.
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.
Fil: Sterkel, Marcos. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Haines, Lee R.. Liverpool School of Tropical Medicine; Reino Unido
Fil: Casas Sánchez, Aitor. Liverpool School of Tropical Medicine; Reino Unido
Fil: Adung'a, Vincent Owino. Egerton University; Kenia. International Centre Of Insect Physiology And Ecology Nairobi; Kenia
Fil: Vionette Amaral, Raquel J.. Liverpool School of Tropical Medicine; Reino Unido
Fil: Quek, Shannon. Liverpool School of Tropical Medicine; Reino Unido
Fil: Rose, Clair. Liverpool School of Tropical Medicine; Reino Unido
Fil: dos Santos, Mariana Silva. Crick Institute; Reino Unido
Fil: Escude, Natalia García. Liverpool School of Tropical Medicine; Reino Unido
Fil: Ismail, Hanafy M.. Liverpool School of Tropical Medicine; Reino Unido
Fil: Paine, Mark I.. Liverpool School of Tropical Medicine; Reino Unido
Fil: Barribeau, Seth M.. University of Liverpool; Reino Unido
Fil: Wagstaff, Simon. Liverpool School of Tropical Medicine; Reino Unido
Fil: MacRae, James I.. Crick Institute; Reino Unido
Fil: Masiga, Daniel. International Centre of Insect Physiology and Ecology; Kenia
Fil: Yakob, Laith. London School of Hygiene and Tropical Medicine; Reino Unido
Fil: Oliveira, Pedro L.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular; Brasil
Fil: Acosta Serrano, Álvaro. Liverpool School of Tropical Medicine; Reino Unido - Materia
-
Glossina morsitans
tyrosine catabolism
HPPD inibition
African trypanosomasis - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/165169
Ver los metadatos del registro completo
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Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasisSterkel, MarcosHaines, Lee R.Casas Sánchez, AitorAdung'a, Vincent OwinoVionette Amaral, Raquel J.Quek, ShannonRose, Clairdos Santos, Mariana SilvaEscude, Natalia GarcíaIsmail, Hanafy M.Paine, Mark I.Barribeau, Seth M.Wagstaff, SimonMacRae, James I.Masiga, DanielYakob, LaithOliveira, Pedro L.Acosta Serrano, ÁlvaroGlossina morsitanstyrosine catabolismHPPD inibitionAfrican trypanosomasishttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Tsetse 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-hydroxyphe-nylpyruvate 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.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.Fil: Sterkel, Marcos. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Haines, Lee R.. Liverpool School of Tropical Medicine; Reino UnidoFil: Casas Sánchez, Aitor. Liverpool School of Tropical Medicine; Reino UnidoFil: Adung'a, Vincent Owino. Egerton University; Kenia. International Centre Of Insect Physiology And Ecology Nairobi; KeniaFil: Vionette Amaral, Raquel J.. Liverpool School of Tropical Medicine; Reino UnidoFil: Quek, Shannon. Liverpool School of Tropical Medicine; Reino UnidoFil: Rose, Clair. Liverpool School of Tropical Medicine; Reino UnidoFil: dos Santos, Mariana Silva. Crick Institute; Reino UnidoFil: Escude, Natalia García. Liverpool School of Tropical Medicine; Reino UnidoFil: Ismail, Hanafy M.. Liverpool School of Tropical Medicine; Reino UnidoFil: Paine, Mark I.. Liverpool School of Tropical Medicine; Reino UnidoFil: Barribeau, Seth M.. University of Liverpool; Reino UnidoFil: Wagstaff, Simon. Liverpool School of Tropical Medicine; Reino UnidoFil: MacRae, James I.. Crick Institute; Reino UnidoFil: Masiga, Daniel. International Centre of Insect Physiology and Ecology; KeniaFil: Yakob, Laith. London School of Hygiene and Tropical Medicine; Reino UnidoFil: Oliveira, Pedro L.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular; BrasilFil: Acosta Serrano, Álvaro. Liverpool School of Tropical Medicine; Reino UnidoPublic Library of Science2021-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/165169Sterkel, Marcos; Haines, Lee R.; Casas Sánchez, Aitor; Adung'a, Vincent Owino; Vionette Amaral, Raquel J.; et al.; Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis; Public Library of Science; PLoS Biology; 19; 1; 1-2021; 1-281544-9173CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pbio.3000796info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000796info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:45Zoai:ri.conicet.gov.ar:11336/165169instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:52:46.077CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis |
| title |
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis |
| spellingShingle |
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis Sterkel, Marcos Glossina morsitans tyrosine catabolism HPPD inibition African trypanosomasis |
| title_short |
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis |
| title_full |
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis |
| title_fullStr |
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis |
| title_full_unstemmed |
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis |
| title_sort |
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis |
| dc.creator.none.fl_str_mv |
Sterkel, Marcos Haines, Lee R. Casas Sánchez, Aitor Adung'a, Vincent Owino Vionette Amaral, Raquel J. Quek, Shannon Rose, Clair dos Santos, Mariana Silva Escude, Natalia García Ismail, Hanafy M. Paine, Mark I. Barribeau, Seth M. Wagstaff, Simon MacRae, James I. Masiga, Daniel Yakob, Laith Oliveira, Pedro L. Acosta Serrano, Álvaro |
| author |
Sterkel, Marcos |
| author_facet |
Sterkel, Marcos Haines, Lee R. Casas Sánchez, Aitor Adung'a, Vincent Owino Vionette Amaral, Raquel J. Quek, Shannon Rose, Clair dos Santos, Mariana Silva Escude, Natalia García Ismail, Hanafy M. Paine, Mark I. Barribeau, Seth M. Wagstaff, Simon MacRae, James I. Masiga, Daniel Yakob, Laith Oliveira, Pedro L. Acosta Serrano, Álvaro |
| author_role |
author |
| author2 |
Haines, Lee R. Casas Sánchez, Aitor Adung'a, Vincent Owino Vionette Amaral, Raquel J. Quek, Shannon Rose, Clair dos Santos, Mariana Silva Escude, Natalia García Ismail, Hanafy M. Paine, Mark I. Barribeau, Seth M. Wagstaff, Simon MacRae, James I. Masiga, Daniel Yakob, Laith Oliveira, Pedro L. Acosta Serrano, Álvaro |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Glossina morsitans tyrosine catabolism HPPD inibition African trypanosomasis |
| topic |
Glossina morsitans tyrosine catabolism HPPD inibition African trypanosomasis |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
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-hydroxyphe-nylpyruvate 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. 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. Fil: Sterkel, Marcos. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Haines, Lee R.. Liverpool School of Tropical Medicine; Reino Unido Fil: Casas Sánchez, Aitor. Liverpool School of Tropical Medicine; Reino Unido Fil: Adung'a, Vincent Owino. Egerton University; Kenia. International Centre Of Insect Physiology And Ecology Nairobi; Kenia Fil: Vionette Amaral, Raquel J.. Liverpool School of Tropical Medicine; Reino Unido Fil: Quek, Shannon. Liverpool School of Tropical Medicine; Reino Unido Fil: Rose, Clair. Liverpool School of Tropical Medicine; Reino Unido Fil: dos Santos, Mariana Silva. Crick Institute; Reino Unido Fil: Escude, Natalia García. Liverpool School of Tropical Medicine; Reino Unido Fil: Ismail, Hanafy M.. Liverpool School of Tropical Medicine; Reino Unido Fil: Paine, Mark I.. Liverpool School of Tropical Medicine; Reino Unido Fil: Barribeau, Seth M.. University of Liverpool; Reino Unido Fil: Wagstaff, Simon. Liverpool School of Tropical Medicine; Reino Unido Fil: MacRae, James I.. Crick Institute; Reino Unido Fil: Masiga, Daniel. International Centre of Insect Physiology and Ecology; Kenia Fil: Yakob, Laith. London School of Hygiene and Tropical Medicine; Reino Unido Fil: Oliveira, Pedro L.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular; Brasil Fil: Acosta Serrano, Álvaro. Liverpool School of Tropical Medicine; Reino Unido |
| description |
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-hydroxyphe-nylpyruvate 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. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-01 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/165169 Sterkel, Marcos; Haines, Lee R.; Casas Sánchez, Aitor; Adung'a, Vincent Owino; Vionette Amaral, Raquel J.; et al.; Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis; Public Library of Science; PLoS Biology; 19; 1; 1-2021; 1-28 1544-9173 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/165169 |
| identifier_str_mv |
Sterkel, Marcos; Haines, Lee R.; Casas Sánchez, Aitor; Adung'a, Vincent Owino; Vionette Amaral, Raquel J.; et al.; Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis; Public Library of Science; PLoS Biology; 19; 1; 1-2021; 1-28 1544-9173 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pbio.3000796 info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000796 |
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application/pdf application/pdf |
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Public Library of Science |
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Public Library of Science |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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