Living microbial therapies have been proposed as a course of action for a variety of diseases. However, problematic interactions between the host immune system and the microbial organism present significant clinical concerns. Previously, we developed a genetically encoded superhydrophilic zwitterionic peptide, termed EKP, to mimic low-immunogenic zwitterionic materials, which have been used for the chemical modification of biologics such as protein and nucleic acid drugs to increase their in vivo circulation time and reduce their immunogenicity. Herein, we demonstrate the protective effects of the EKP polypeptide genetically cloaking the surface of Saccharomyces cerevisiae as a model microbe in both in vitro and in vivo systems. First, we show that EKP peptide cloaking suppresses the interactions between yeast cells and their specific antibodies, thereby illustrating its cloaking behavior. Then, we examine the in vitro interactions between EKP peptide surface cloaked yeast cells and murine macrophage cells, which exhibit phagocytotic behavior in the presence of foreign microbes. Our results indicate that EKP cloaking suppresses macrophage interactions and thus reduces phagocytosis. Furthermore, EKP cloaked yeast cells demonstrate a prolonged circulation time in mice in vivo.

中文翻译：

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用两性离子肽钝化活微生物的背景进行治疗

活微生物疗法已被提议作为多种疾病的治疗方案。然而，宿主免疫系统和微生物之间存在问题的相互作用提出了重大的临床问题。此前，我们开发了一种基因编码的超亲水性两性离子肽，称为EKP，来模拟低免疫原性两性离子材料，该材料已用于蛋白质和核酸药物等生物制剂的化学修饰，以增加其体内循环时间并降低其免疫原性。在此，我们在体外和体内系统中证明了 EKP 多肽在基因上覆盖作为模型微生物的酿酒酵母表面的保护作用。首先，我们证明 EKP 肽隐藏会抑制酵母细胞与其特异性抗体之间的相互作用，从而说明其隐藏行为。然后，我们检查了 EKP 肽表面覆盖的酵母细胞和鼠巨噬细胞之间的相互作用，这些细胞在外来微生物存在的情况下表现出吞噬行为。我们的结果表明 EKP 隐藏抑制巨噬细胞相互作用，从而减少吞噬作用。此外，EKP 包裹的酵母细胞在小鼠体内表现出延长的循环时间。