Targeting the tsetse-trypanosome interplay using genetically engineered Sodalis glossinidius
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 ta...
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| Veröffentlicht in: | PLoS pathogens 2022-03, Vol.18 (3), p.e1010376-e1010376 |
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| creator | De Vooght, Linda De Ridder, Karin Hussain, Shahid Stijlemans, Benoît De Baetselier, Patrick Caljon, Guy Van Den Abbeele, Jan |
| description | 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. |
| doi_str_mv | 10.1371/journal.ppat.1010376 |
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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. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Vooght, Linda</au><au>De Ridder, Karin</au><au>Hussain, Shahid</au><au>Stijlemans, Benoît</au><au>De Baetselier, Patrick</au><au>Caljon, Guy</au><au>Van Den Abbeele, Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting the tsetse-trypanosome interplay using genetically engineered Sodalis glossinidius</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>18</volume><issue>3</issue><spage>e1010376</spage><epage>e1010376</epage><pages>e1010376-e1010376</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35271685</pmid><doi>10.1371/journal.ppat.1010376</doi><tpages>e1010376</tpages><orcidid>https://orcid.org/0000-0002-8425-8601</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | African trypanosomiasis Animals Antibiotics Biology and Life Sciences Crosstalk Developmental stages Diptera Enterobacteriaceae - genetics Enterobacteriaceae - metabolism Exocrine glands Gene expression Genetic aspects Genetic engineering Health aspects Host-parasite relationships Infections Libraries Load distribution Medicine and Health Sciences Midgut Nanobodies Panning Parasites Parasitic diseases Research and Analysis Methods Single-Domain Antibodies - metabolism Symbiosis Trypanosoma Trypanosoma brucei Trypanosoma brucei brucei - genetics Trypanosome Tsetse Flies - parasitology Vectors (Biology) |
| title | Targeting the tsetse-trypanosome interplay using genetically engineered Sodalis glossinidius |
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