Open AccessTargeting the tsetse-trypanosome interplay using genetically engineered Sodalis glossinidius
Author(s) -
Linda De Vooght,
Karin De Ridder,
Shahid Hussain,
Benoı̂t Stijlemans,
Patrick De Baetseĺier,
Guy Caljon,
Jan Van Den Abbeele
Publication year - 2022
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1010376
Subject(s) - trypanosoma brucei , tsetse fly , midgut , biology , effector , vector (molecular biology) , parasite hosting , african trypanosomiasis , trypanosoma , computational biology , trypanosomiasis , microbiology and biotechnology , virology , gene , genetics , recombinant dna , botany , larva , world wide web , computer science
Sodalis glossinidius , a secondary bacterial symbiont of the tsetse fly, is currently considered as a potential delivery system for anti-trypanosomal components interfering with African trypanosome transmission ( i . e . paratransgenesis). Nanobodies (Nbs) have been proposed as potential candidates to target the parasite during development in the tsetse fly. In this study, we have generated an immune Nb-library and developed a panning strategy to select Nbs against the Trypanosoma brucei brucei procyclic developmental stage present in the tsetse fly midgut. Selected Nbs were expressed, purified, assessed for binding and tested for their impact on the survival and growth of in vitro cultured procyclic T . b . brucei parasites. Next, we engineered S . glossinidius to express the selected Nbs and validated their ability to block T . brucei development in the tsetse fly midgut. Genetically engineered S . glossinidius expressing Nb_88 significantly compromised parasite development in the tsetse fly midgut both at the level of infection rate and parasite load. Interestingly, expression of Nb_19 by S . glossinidius resulted in a significantly enhanced midgut establishment. These data are the first to show in situ delivery by S . glossinidius of effector molecules that can target the trypanosome-tsetse fly crosstalk, interfering with parasite development in the fly. These proof-of-principle data represent a major step forward in the development of a control strategy based on paratransgenic tsetse flies. Finally, S . glossinidius -based Nb delivery can also be applied as a powerful laboratory tool to unravel the molecular determinants of the parasite-vector association.