Chamas Alexandre, Svensson Carl-Magnus, Maneira Carla, Sporniak Marta, Figge Marc Thilo, Lackner Gerald
Junior Research Group Synthetic Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology, Jena 07745, Germany.
Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena 07743, Germany.
ACS Synth Biol. 2024 Dec 20;13(12):4027-4039. doi: 10.1021/acssynbio.4c00466. Epub 2024 Sep 12.
Engineering live biotherapeutic products against fungal pathogens such as has been suggested as a means to tackle the increasing threat of fungal infections and the development of resistance to classical antifungal treatments. One important challenge in the design of live therapeutics is to control their localization inside the human body. The specific binding capability to target organisms or tissues would greatly increase their effectiveness by increasing the local concentration of effector molecules at the site of infection. In this study, we utilized surface display of carbohydrate binding domains to enable the probiotic Nissle 1917 to adhere specifically to the pathogenic yeast . Binding was quantified using a newly developed method based on the automated analysis of microscopic images. In addition to a rationally selected chitin binding domain, a synthetic peptide of identical length but distinct sequence also conferred binding. Efficient binding was specific to fungal hyphae, the invasive form of , while the yeast form, as well as abiotic cellulose and PET particles, was only weakly recognized.
设计针对真菌病原体（如 ）的活体生物治疗产品，已被认为是应对真菌感染日益增加的威胁以及对传统抗真菌治疗产生耐药性的一种手段。设计活体治疗药物的一个重要挑战是控制它们在人体内的定位。对靶标生物体或组织的特异性结合能力，通过增加感染部位效应分子的局部浓度，将大大提高其有效性。在本研究中，我们利用碳水化合物结合结构域的表面展示，使益生菌Nissle 1917能够特异性粘附于致病性酵母 。使用基于显微镜图像自动分析的新开发方法对结合进行定量。除了合理选择的几丁质结合结构域之外，相同长度但不同序列的合成肽也赋予了结合能力。高效结合对真菌菌丝（即 的侵袭形式）具有特异性，而酵母形式以及非生物纤维素和PET颗粒仅被微弱识别。
