Waldrip Zachary J, Burdine Lyle, Peterson Eric C, Rainwater Randall R, Min Yoobin, Burdine Marie Shluterman
Arkansas Children's Research Institute, Little Rock, AR 72202, USA.
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
iScience. 2025 Aug 6;28(9):113303. doi: 10.1016/j.isci.2025.113303. eCollection 2025 Sep 19.
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 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 that 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.
利用工程微生物治疗胃肠道疾病等病症存在尚未开发的潜力。在本报告中，我们探讨了将成熟的蛋白质表面展示方法用于益生菌酵母，以在模拟胃肠道环境中展示抗体的可行性。我们证明，这种直接源自商业益生菌的酵母营养缺陷型菌株能够表达锚定在细胞表面的功能性抗体。我们发现，这些与细胞壁相连的抗体能够在生理温度和模拟结肠液中结合其靶抗原，模拟了口服摄入的益生菌酵母可能遇到微生物产生的毒素或其他生物分子的人体环境。我们还证明，这种方法对抗原的亚纳摩尔浓度敏感，这表明展示抗体的酵母细胞有可能有效地结合极低浓度的靶标。
