Cargando…

Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro

East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen Theileria parva. The disease is a major problem for cattle farmers in affected regions and there are few methods of control, including a complex infection and treatment vaccine,...

Descripción completa

Detalles Bibliográficos
Autores principales: Steketee, Pieter C., Paxton, Edith, Barrett, Michael P., Pearce, Michael C., Connelley, Timothy K., Morrison, Liam J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623109/
https://www.ncbi.nlm.nih.gov/pubmed/37866107
http://dx.doi.org/10.1016/j.ijpddr.2023.10.003
_version_ 1785130678484992000
author Steketee, Pieter C.
Paxton, Edith
Barrett, Michael P.
Pearce, Michael C.
Connelley, Timothy K.
Morrison, Liam J.
author_facet Steketee, Pieter C.
Paxton, Edith
Barrett, Michael P.
Pearce, Michael C.
Connelley, Timothy K.
Morrison, Liam J.
author_sort Steketee, Pieter C.
collection PubMed
description East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen Theileria parva. The disease is a major problem for cattle farmers in affected regions and there are few methods of control, including a complex infection and treatment vaccine, expensive chemotherapy, and the more widespread tick control through acaricides. New intervention strategies are, therefore, sorely needed. Benzoxaboroles are a versatile class of boron-heterocyclic compounds with demonstrable pharmacological activity against a diverse group of pathogens, including those related to T. parva. In this study, the in vitro efficacy of three benzoxaboroles against the intracellular schizont stage of T. parva was investigated using a flow cytometry approach. Of the benzoxaboroles tested, only one showed any potency, albeit only at high concentrations, even though there is high protein sequence similarity in the CPSF3 protein target compared to other protozoan pathogen species. This finding suggests that benzoxaboroles currently of interest for the treatment of African animal trypanosomiasis, toxoplasmosis, cryptosporidiosis and malaria may not be suitable for the treatment of ECF. We conclude that testing of further benzoxaborole compounds is needed to fully determine whether any lead compounds can be identified to target T. parva.
format Online
Article
Text
id pubmed-10623109
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-106231092023-11-04 Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro Steketee, Pieter C. Paxton, Edith Barrett, Michael P. Pearce, Michael C. Connelley, Timothy K. Morrison, Liam J. Int J Parasitol Drugs Drug Resist Regular article East Coast Fever (ECF) is a disease affecting cattle in sub-Saharan Africa, caused by the tick-borne Apicomplexan pathogen Theileria parva. The disease is a major problem for cattle farmers in affected regions and there are few methods of control, including a complex infection and treatment vaccine, expensive chemotherapy, and the more widespread tick control through acaricides. New intervention strategies are, therefore, sorely needed. Benzoxaboroles are a versatile class of boron-heterocyclic compounds with demonstrable pharmacological activity against a diverse group of pathogens, including those related to T. parva. In this study, the in vitro efficacy of three benzoxaboroles against the intracellular schizont stage of T. parva was investigated using a flow cytometry approach. Of the benzoxaboroles tested, only one showed any potency, albeit only at high concentrations, even though there is high protein sequence similarity in the CPSF3 protein target compared to other protozoan pathogen species. This finding suggests that benzoxaboroles currently of interest for the treatment of African animal trypanosomiasis, toxoplasmosis, cryptosporidiosis and malaria may not be suitable for the treatment of ECF. We conclude that testing of further benzoxaborole compounds is needed to fully determine whether any lead compounds can be identified to target T. parva. Elsevier 2023-10-10 /pmc/articles/PMC10623109/ /pubmed/37866107 http://dx.doi.org/10.1016/j.ijpddr.2023.10.003 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Regular article
Steketee, Pieter C.
Paxton, Edith
Barrett, Michael P.
Pearce, Michael C.
Connelley, Timothy K.
Morrison, Liam J.
Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro
title Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro
title_full Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro
title_fullStr Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro
title_full_unstemmed Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro
title_short Anti-parasitic benzoxaboroles are ineffective against Theileria parva in vitro
title_sort anti-parasitic benzoxaboroles are ineffective against theileria parva in vitro
topic Regular article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623109/
https://www.ncbi.nlm.nih.gov/pubmed/37866107
http://dx.doi.org/10.1016/j.ijpddr.2023.10.003
work_keys_str_mv AT steketeepieterc antiparasiticbenzoxaborolesareineffectiveagainsttheileriaparvainvitro
AT paxtonedith antiparasiticbenzoxaborolesareineffectiveagainsttheileriaparvainvitro
AT barrettmichaelp antiparasiticbenzoxaborolesareineffectiveagainsttheileriaparvainvitro
AT pearcemichaelc antiparasiticbenzoxaborolesareineffectiveagainsttheileriaparvainvitro
AT connelleytimothyk antiparasiticbenzoxaborolesareineffectiveagainsttheileriaparvainvitro
AT morrisonliamj antiparasiticbenzoxaborolesareineffectiveagainsttheileriaparvainvitro