A Trojan Horse to fight disease…

Originally appearing at endtheneglect.org

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From an ancient Latin poem comes the relatively simple concept — deliver the deadly blow within a Trojan horse. The Greeks used it to end the war against Troy after ten long years. In science it’s one of the new and unique ways scientists are coming up with to fight diseases in man. To fight the disease before it gets into the host — in the animals that transmit and spread such diseases. The goal to eliminate the disease within the fly by using something common to the fly — the bacteria that lies within. It’s a common theme that is gaining popularity. In science we call it paratransgenesis. A strategy that relies on weaponizing the simple bacteria that live inside the flies that transmit parasites.

New open access research published in BioMed Central’s Microbial Cell Factories uses such a trojan horse paratransgenesis technique that represents a new way researchers are looking to fight African sleeping sickness.

The same way there are bacteria within our gut and digestive system — aiding our digestion, providing the nutrients that we are unable to synthesize ourselves, and generally contributing to our being — the tsetse fly also contains bacteria (bacterial endosymbiont). Sodalis glossinidius is one such bacteria.

The bacterial endosymbiont of the tsetse fly can be found in many places within the tsetse fly. Both inter- and intracellularly in the fly midgut, muscle, fat body, milk glands, and salivary glands. They can be found everywhere in the fly, but more importantly, everywhere that counts — everywhere the trypanosome invades. That seems to be the great advantage of using this bacteria as a delivery mechanism.

With this bacteria, which naturally lives in the tsetse fly, the researchers working in Belgium have been able to turn the bacteria against the trypanosome. They modified the bacteria’s genome to secrete a single domain antibody. These antibodies, which bind to the surface of the parasite, are the first stage in producing targeted nanobodies which could kill, or block, trypanosome development.

The technique proved tricky, and a delicate one to get right. The most important factor was that the growth of the mutated bacteria was unaltered, increasing their chances of survival within the fly, and meaning the trypanosome had less of a chance to overcome the attack.

Such a technique has already been done for other diseases of note — dengue, malaria, and Chagas disease. More and more, the foundation is being laid for a new kind of disease prevention strategy.

ResearchBlogging.org

Coutinho-Abreu, I., Zhu, K., & Ramalho-Ortigao, M. (2010). Transgenesis and paratransgenesis to control insect-borne diseases: Current status and future challenges Parasitology International, 59 (1), 1-8 DOI: 10.1016/j.parint.2009.10.002

De Vooght, L., Caljon, G., Stijlemans, B., De Beatselier, P., Coosemans, M., & Van Den Abbeele, J. (2012). Expression and extracellular release of a functional anti-trypanosome Nanobody(R) in Sodalis glossinidius, a bacterial symbiont of the tsetse fly Microbial Cell Factories, 11 (1) DOI: 10.1186/1475-2859-11-23

Durvasula RV, Gumbs A, Panackal A, Kruglov O, Aksoy S, Merrifield RB, Richards FF, & Beard CB (1997). Prevention of insect-borne disease: an approach using transgenic symbiotic bacteria. Proceedings of the National Academy of Sciences of the United States of America, 94 (7), 3274-8 PMID: 9096383

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