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一种生物响应性遗传编码抗菌晶体，用于治疗幽门螺杆菌感染的口服治疗。

A Bioresponsive Genetically Encoded Antimicrobial Crystal for the Oral Treatment of Helicobacter Pylori Infection.

机构信息

School of Life Sciences and Center of Novel Biomaterials, The Chinese University of Hong Kong, Hong Kong, 999077, China.

Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 999077, China.

出版信息

Adv Sci (Weinh). 2023 Oct;10(30):e2301724. doi: 10.1002/advs.202301724. Epub 2023 Sep 7.

DOI:10.1002/advs.202301724
PMID:37675807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10602570/
Abstract

Helicobacter pylori (H. pylori) causes infection in the stomach and is a major factor for gastric carcinogenesis. The application of antimicrobial peptides (AMPs) as an alternative treatment to traditional antibiotics is limited by their facile degradation in the stomach, their poor penetration of the gastric mucosa, and the cost of peptide production. Here, the design and characterization of a genetically encoded H. pylori-responsive microbicidal protein crystal Cry3Aa-MIIA-AMP-P17 is described. This designed crystal exhibits preferential binding to H. pylori, and when activated, promotes the targeted release of the AMP at the H. pylori infection site. Significantly, when the activated Cry3Aa-MIIA-AMP-P17 crystals are orally delivered to infected mice, the Cry3Aa crystal framework protects its cargo AMP against degradation, resulting in enhanced in vivo efficacy against H. pylori infection. Notably, in contrast to antibiotics, treatment with the activated crystals results in minimal perturbation of the mouse gut microbiota. These results demonstrate that engineered Cry3Aa crystals can serve as an effective platform for the oral delivery of therapeutic peptides to treat gastrointestinal diseases.

摘要

幽门螺杆菌（H. pylori）会在胃部引发感染，是导致胃癌的主要因素。抗菌肽（AMPs）作为传统抗生素的替代疗法的应用受到限制，这是因为它们在胃部容易降解，难以穿透胃黏膜，而且肽类的生产成本也很高。本研究设计并表征了一种基因编码的、对幽门螺杆菌有响应的杀菌蛋白晶体 Cry3Aa-MIIA-AMP-P17。这种设计的晶体对幽门螺杆菌具有优先结合性，当被激活时，能够在幽门螺杆菌感染部位靶向释放 AMP。重要的是，当口服给予感染的小鼠激活的 Cry3Aa-MIIA-AMP-P17 晶体时，Cry3Aa 晶体骨架能够保护其携带的 AMP 免受降解，从而增强了体内对抗幽门螺杆菌感染的疗效。值得注意的是，与抗生素治疗相比，激活晶体的治疗作用对小鼠肠道微生物群的干扰最小。这些结果表明，经过工程改造的 Cry3Aa 晶体可以作为一种有效的口服递送治疗性肽的平台，用于治疗胃肠道疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/d13003c7d4e6/ADVS-10-2301724-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/e6bbce17dd10/ADVS-10-2301724-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/8689ea961bd1/ADVS-10-2301724-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/fe5a99d96b7c/ADVS-10-2301724-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/ac3d949be126/ADVS-10-2301724-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/3c472b7f8ba1/ADVS-10-2301724-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/e8207e757dc3/ADVS-10-2301724-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/56b18137e4d2/ADVS-10-2301724-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/d13003c7d4e6/ADVS-10-2301724-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/e6bbce17dd10/ADVS-10-2301724-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/8689ea961bd1/ADVS-10-2301724-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/fe5a99d96b7c/ADVS-10-2301724-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/ac3d949be126/ADVS-10-2301724-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/3c472b7f8ba1/ADVS-10-2301724-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/e8207e757dc3/ADVS-10-2301724-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/56b18137e4d2/ADVS-10-2301724-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dca/10602570/d13003c7d4e6/ADVS-10-2301724-g003.jpg

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