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Targeting cattle-borne zoonoses and cattle pathogens using a novel trypanosomatid-based delivery system

Authors :
Ailie Robinson
Raymond Wilson
Jacqueline B. Matthews
Dick Schaap
G. Adam Mott
Anuruddika Fernando
David Kennedy
Paula MacGregor
Keith R. Matthews
Source :
PLoS Pathogens, PLoS Pathogens, Vol 7, Iss 10, p e1002340 (2011), Mott, G A, Wilson, R, Fernando, A, Robinson, A, MacGregor, P, Kennedy, D, Schaap, D, Matthews, J B & Matthews, K R 2011, ' Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System ', PLoS Pathogens, vol. 7, no. 10, e1002340 . https://doi.org/10.1371/journal.ppat.1002340
Publication Year :
2011

Abstract

Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis.<br />Author Summary Single-celled parasites of the order Kinetoplastida are responsible for devastating diseases of humans and animals, including African trypanosomiasis, Chagas' disease and leishmaniasis. However, there are also many species of trypanosomatids that do not cause disease and are distributed globally. One example is Trypanosoma (Megatrypanum) theileri, which is restricted to bovids and ubiquitous in cattle herds worldwide. This organism is maintained extracellularly in the blood and tissues long-term without any observed ill effects on host health or productivity. Using knowledge of gene expression and protein trafficking in pathogenic trypanosomatids, we have successfully developed, from first principles, Trypanosoma theileri as a delivery system for vaccine antigens and therapeutics. Procedures for the growth, transfection and heterologous gene expression of T. theileri have been developed, and the delivery of a vaccine antigen derived from Babesia divergens evaluated in vivo. Our results demonstrate the ability of T. theileri to be used as a flexible and easily manipulated protein delivery system suitable for the control of cattle pathogens and cattle-borne zoonoses. In one notable application, we propose that the system could allow the expression of serum trypanolytic factors in cattle, with the potential to alleviate poverty in Africa through the killing of pathogenic trypanosomatids in livestock.

Details

ISSN :
15537374 and 15537366
Volume :
7
Issue :
10
Database :
OpenAIRE
Journal :
PLoS pathogens
Accession number :
edsair.doi.dedup.....d2b3288fb99e34e54e754c318d48ade0
Full Text :
https://doi.org/10.1371/journal.ppat.1002340