Cargando…

Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius

BACKGROUND: Sodalis glossinidius, a vertically transmitted microbial symbiont of the tsetse fly, is currently considered as a potential delivery system for anti-trypanosomal components that reduce or eliminate the capability of the tsetse fly host to transmit parasitic trypanosomes, an approach also...

Descripción completa

Detalles Bibliográficos
Autores principales: De Vooght, Linda, Caljon, Guy, De Ridder, Karin, Van Den Abbeele, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230353/
https://www.ncbi.nlm.nih.gov/pubmed/25376234
http://dx.doi.org/10.1186/s12934-014-0156-6
_version_ 1782344254913249280
author De Vooght, Linda
Caljon, Guy
De Ridder, Karin
Van Den Abbeele, Jan
author_facet De Vooght, Linda
Caljon, Guy
De Ridder, Karin
Van Den Abbeele, Jan
author_sort De Vooght, Linda
collection PubMed
description BACKGROUND: Sodalis glossinidius, a vertically transmitted microbial symbiont of the tsetse fly, is currently considered as a potential delivery system for anti-trypanosomal components that reduce or eliminate the capability of the tsetse fly host to transmit parasitic trypanosomes, an approach also known as paratransgenesis. An essential step in developing paratransgenic tsetse is the stable colonization of adult flies and their progeny with recombinant Sodalis bacteria, expressing trypanocidal effector molecules in tissues where the parasite resides. RESULTS: In this study, Sodalis was tested for its ability to deliver functional anti-trypanosome nanobodies (Nbs) in Glossina morsitans morsitans. We characterized the in vitro and in vivo stability of recombinant Sodalis (recSodalis) expressing a potent trypanolytic nanobody, i.e. Nb_An46. We show that recSodalis is competitive with WT Sodalis in in vivo conditions and that tsetse flies transiently cleared of their endogenous WT Sodalis population can be successfully repopulated with recSodalis at high densities. In addition, vertical transmission to the offspring was observed. Finally, we demonstrated that recSodalis expressed significant levels (ng range) of functional Nb_An46 in different tsetse fly tissues, including the midgut where an important developmental stage of the trypanosome parasite occurs. CONCLUSIONS: We demonstrated the proof-of-concept that the Sodalis symbiont can be genetically engineered to express and release significant amounts of functional anti-trypanosome Nbs in different tissues of the tsetse fly. The application of this innovative concept of using pathogen-targeting nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-014-0156-6) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4230353
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-42303532014-11-14 Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius De Vooght, Linda Caljon, Guy De Ridder, Karin Van Den Abbeele, Jan Microb Cell Fact Research BACKGROUND: Sodalis glossinidius, a vertically transmitted microbial symbiont of the tsetse fly, is currently considered as a potential delivery system for anti-trypanosomal components that reduce or eliminate the capability of the tsetse fly host to transmit parasitic trypanosomes, an approach also known as paratransgenesis. An essential step in developing paratransgenic tsetse is the stable colonization of adult flies and their progeny with recombinant Sodalis bacteria, expressing trypanocidal effector molecules in tissues where the parasite resides. RESULTS: In this study, Sodalis was tested for its ability to deliver functional anti-trypanosome nanobodies (Nbs) in Glossina morsitans morsitans. We characterized the in vitro and in vivo stability of recombinant Sodalis (recSodalis) expressing a potent trypanolytic nanobody, i.e. Nb_An46. We show that recSodalis is competitive with WT Sodalis in in vivo conditions and that tsetse flies transiently cleared of their endogenous WT Sodalis population can be successfully repopulated with recSodalis at high densities. In addition, vertical transmission to the offspring was observed. Finally, we demonstrated that recSodalis expressed significant levels (ng range) of functional Nb_An46 in different tsetse fly tissues, including the midgut where an important developmental stage of the trypanosome parasite occurs. CONCLUSIONS: We demonstrated the proof-of-concept that the Sodalis symbiont can be genetically engineered to express and release significant amounts of functional anti-trypanosome Nbs in different tissues of the tsetse fly. The application of this innovative concept of using pathogen-targeting nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-014-0156-6) contains supplementary material, which is available to authorized users. BioMed Central 2014-11-07 /pmc/articles/PMC4230353/ /pubmed/25376234 http://dx.doi.org/10.1186/s12934-014-0156-6 Text en © De Vooght et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
De Vooght, Linda
Caljon, Guy
De Ridder, Karin
Van Den Abbeele, Jan
Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius
title Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius
title_full Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius
title_fullStr Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius
title_full_unstemmed Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius
title_short Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius
title_sort delivery of a functional anti-trypanosome nanobody in different tsetse fly tissues via a bacterial symbiont, sodalis glossinidius
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230353/
https://www.ncbi.nlm.nih.gov/pubmed/25376234
http://dx.doi.org/10.1186/s12934-014-0156-6
work_keys_str_mv AT devooghtlinda deliveryofafunctionalantitrypanosomenanobodyindifferenttsetseflytissuesviaabacterialsymbiontsodalisglossinidius
AT caljonguy deliveryofafunctionalantitrypanosomenanobodyindifferenttsetseflytissuesviaabacterialsymbiontsodalisglossinidius
AT deridderkarin deliveryofafunctionalantitrypanosomenanobodyindifferenttsetseflytissuesviaabacterialsymbiontsodalisglossinidius
AT vandenabbeelejan deliveryofafunctionalantitrypanosomenanobodyindifferenttsetseflytissuesviaabacterialsymbiontsodalisglossinidius