Targeting the tsetse-trypanosome interplay using genetically engineered Sodalis glossinidius.

Area of Science:

• Vector biology
• Microbial symbiosis
• Parasitology

Background:

• Sodalis glossinidius, a tsetse fly symbiont, is explored for paratransgenesis to combat African trypanosomiasis.
• Nanobodies (Nbs) are investigated as effector molecules to target Trypanosoma brucei development within the fly.

Purpose of the Study:

• To select and engineer nanobodies (Nbs) targeting Trypanosoma brucei in the tsetse fly midgut.
• To validate the efficacy of engineered Sodalis glossinidius in delivering Nbs for parasite control.

Main Methods:

• Generation of an immune Nb-library and panning for Nbs against T. b. brucei.
• Expression and purification of selected Nbs; assessment of binding and anti-parasitic activity in vitro.
• Engineering S. glossinidius to express Nbs and evaluating their impact on T. b. brucei development in tsetse flies.

Main Results:

• Engineered S. glossinidius expressing Nb_88 significantly reduced T. b. brucei infection rates and parasite load in tsetse flies.
• Nb_19 expression by S. glossinidius led to enhanced midgut parasite establishment, indicating stage-specific effects.
• Demonstrated in situ delivery of effector molecules by S. glossinidius targeting trypanosome-tsetse fly interactions.

Conclusions:

• S. glossinidius-mediated Nb delivery is a viable strategy for paratransgenic control of African trypanosomiasis.
• This approach offers a novel tool to study parasite-vector associations and develop disease control methods.