Title
Expression and extracellular release of a functional anti-trypanosome Nanobody® in **Sodalis glossinidius**, a bacterial symbiont of the tsetse fly Expression and extracellular release of a functional anti-trypanosome Nanobody® in **Sodalis glossinidius**, a bacterial symbiont of the tsetse fly
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
London ,
Subject
Biology
Human medicine
Engineering sciences. Technology
Source (journal)
Microbial cell factories. - London
Volume/pages
11(2012) , 11 p.
ISSN
1475-2859
1475-2859
Article Reference
23
Carrier
E-only publicatie
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Background Sodalis glossinidius, a gram-negative bacterial endosymbiont of the tsetse fly, has been proposed as a potential in vivo drug delivery vehicle to control trypanosome parasite development in the fly, an approach known as paratransgenesis. Despite this interest of S. glossinidius as a paratransgenic platform organism in tsetse flies, few potential effector molecules have been identified so far and to date none of these molecules have been successfully expressed in this bacterium. Results In this study, S. glossinidius was transformed to express a single domain antibody, (Nanobody®) Nb_An33, that efficiently targets conserved cryptic epitopes of the variant surface glycoprotein (VSG) of the parasite Trypanosoma brucei. Next, we analyzed the capability of two predicted secretion signals to direct the extracellular delivery of significant levels of active Nb_An33. We show that the pelB leader peptide was successful in directing the export of fully functional Nb_An33 to the periplasm of S. glossinidius resulting in significant levels of extracellular release. Finally, S. glossinidius expressing pelBNb_An33 exhibited no significant reduction in terms of fitness, determined by in vitro growth kinetics, compared to the wild-type strain. Conclusions These data are the first demonstration of the expression and extracellular release of functional trypanosome-interfering Nanobodies® in S. glossinidius. Furthermore, Sodalis strains that efficiently released the effector protein were not affected in their growth, suggesting that they may be competitive with endogenous microbiota in the midgut environment of the tsetse fly. Collectively, these data reinforce the notion for the potential of S. glossinidius to be developed into a paratransgenic platform organism.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/12d80b/8adc6d42.pdf
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