The National Institutes of Health (NIH) has awarded a $1,333,682 Project Grant under the Trans-NIH Research Support program (CFDA 93.310) to North Carolina State University (NC State) to develop peptide inhibitors that neutralize bacterial toxins and deliver them using engineered probiotic yeast. This 3-year project aims to expand on NC State's previous work identifying a lead peptide inhibitor of Clostridioides difficile toxin, by screening for inhibitors of 5 additional bacterial toxins. The potency and mechanism of action of promising peptide leads will be evaluated in cell-based and in vitro assays. These peptides will then be encoded in the genome of probiotic yeast strains to enable continuous on-site biomanufacturing and display of toxin-binding proteins on the yeast cell surface to sequester toxins. The efficacy of the peptide inhibitors and yeast delivery vectors will be assessed in animal models, with the goal of prolonging the utility of existing antibacterial drugs.