PDF(Pubmed)
Abstract：
BACKGROUND: Type I interferons (IFN-I)-a group of cytokines with immunomodulatory, antiproliferative, and antiviral properties-are widely used as therapeutics for various cancers and viral diseases. Since IFNs are proteins, they are highly susceptible to degradation by proteases and by hydrolysis in the strong acid environment of the stomach, and they are therefore administered parenterally. In this study, we examined whether the intestinal bacterium, enteropathogenic Escherichia coli (EPEC), can be exploited for oral delivery of IFN-Is. EPEC survives the harsh conditions of the stomach and, upon reaching the small intestine, expresses a type III secretion system (T3SS) that is used to translocate effector proteins across the bacterial envelope into the eukaryotic host cells.
RESULTS: In this study, we developed an attenuated EPEC strain that cannot colonize the host but can secrete functional human IFNα2 variant through the T3SS. We found that this bacteria-secreted IFN exhibited antiproliferative and antiviral activities similar to commercially available IFN.
CONCLUSIONS: These findings present a potential novel approach for the oral delivery of IFN via secreting bacteria.
RESULTS: In this study, we developed an attenuated EPEC strain that cannot colonize the host but can secrete functional human IFNα2 variant through the T3SS. We found that this bacteria-secreted IFN exhibited antiproliferative and antiviral activities similar to commercially available IFN.
CONCLUSIONS: These findings present a potential novel approach for the oral delivery of IFN via secreting bacteria.
摘要：
背景：I型干扰素（IFN-I）-一组具有免疫调节功能的细胞因子，抗增殖,和抗病毒特性-广泛用作各种癌症和病毒性疾病的治疗剂。由于IFN是蛋白质，它们极易被蛋白酶和在胃的强酸环境中水解降解，因此它们是肠胃外给药的。在这项研究中,我们检查了肠道细菌，肠致病性大肠杆菌（EPEC），可用于口服递送IFN-Is。EPEC在恶劣的胃部条件下幸存下来，到达小肠后，表达III型分泌系统（T3SS），该系统用于将效应蛋白跨细菌包膜转移到真核宿主细胞中。
结果：在这项研究中，我们开发了一种减毒的EPEC菌株，该菌株不能定殖宿主，但可以通过T3SS分泌功能性人IFNα2变体。我们发现这种细菌分泌的IFN表现出与市售IFN相似的抗增殖和抗病毒活性。
结论：这些发现为通过分泌细菌口服递送IFN提供了一种潜在的新方法。
结果：在这项研究中，我们开发了一种减毒的EPEC菌株，该菌株不能定殖宿主，但可以通过T3SS分泌功能性人IFNα2变体。我们发现这种细菌分泌的IFN表现出与市售IFN相似的抗增殖和抗病毒活性。
结论：这些发现为通过分泌细菌口服递送IFN提供了一种潜在的新方法。
