Congrats to Ilia Gelfat, M.B. Avinash, Hann Tu, and all the other co-authors on our new paper out in PLoS Pathogens! The paper describes the use of engineered protein (curli) fibers, produced by a probiotic bacterium to block the infection of enteric pathogens. We could not have done this work without our amazing Tufts collaborators: Chuck Shoemaker (Cummings Vet School) and John Leong (Tufts Medical School) and their respective group members. They started a project to create enteric pathogen-inactivating camelid antibodies many years ago, funded by the Gates Foundation.The antibodies worked well to block pathogens from infecting, but there was not a good way to deliver them to the gastrointestinal tract, where they need to act. We linked up with John and Chuck to figure out a way to make the antibodies using an engineered probiotic bacterium. Not only did we show that the bacterium can secrete the antibodies, we programmed it to attach them to a protein nanofiber network that it also makes. This results in a “net” that can be customized to trap specific pathogens through the antibodies. Our results show that the antibody-decorated curli “net” works in vitro to block the ability of virulent pathogens to harm cells. With the amazing toolbox of antibodies that can bind several top global pathogens associated with enteric disease, we have a versatile therapeutic approach that is easily customized, can be delivered orally, and maintains a high local concentration of therapeutic antibodies. In vivo validation is still ongoing, but we think this is a unique and promising platform. Diarrhea caused by enteric pathogens remains the 2nd most prevalent cause of death for children under age 5 in the world. Our approach is compatible with many of the requirements for an effective solution – easy to manufacture and distribute compared to conventional drugs and vaccines, minimal refrigeration requirements, orally delivered, cheap to produce.

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