A functional surface display system in Saccharomyces boulardii for protein absorption in simulated intestinal fluids

There is untapped potential for medical breakthroughs using engineered microbes to treat conditions such as those of the gastrointestinal tract. In this report, we explore the feasibility of established protein surface display methods to be used in the probiotic yeast Saccharomyces boulardii to display antibodies within a simulated gastrointestinal environment. We demonstrate that an auxotrophic strain of this yeast derived directly from a commercial probiotic can express functional antibodies tethered to the cell surface. We found these cell wall-tethered antibodies are able to bind their target antigen at physiological temperature and in simulated colonic fluids, mimicking the conditions in the human body where an orally ingested probiotic yeast may encounter microbially generated toxins or other biomolecules. We also demonstrate that this approach is sensitive to sub-nanomolar concentrations of antigen, providing evidence that an antibody-displaying yeast cell can potentially be effective at binding very low concentrations of target.