Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland.
Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland.
Curr Opin Biotechnol. 2021 Apr;68:51-59. doi: 10.1016/j.copbio.2020.09.012. Epub 2020 Oct 27.
The rapid emergence of antibiotic-resistant bacteria and the lack of novel antibacterial agents pose a serious threat for patients and healthcare systems. Bacteriophage-encoded peptidoglycan hydrolases (endolysins) represent a promising new class of antimicrobials. Over the past two decades, research on these enzymes has evolved from basic in vitro characterization to sophisticated protein engineering approaches, including advanced preclinical and clinical testing. In recent years, increasingly specific animal models have shown efficacy of endolysins against bacterial infections of various different organs and tissues of the body. Despite these advances, some challenges with regard to systemic application of endolysins remain to be addressed. These include immunogenicity, circulation half-life, and cell and tissue-specific targeting and penetration properties.
抗生素耐药菌的迅速出现以及新型抗菌药物的缺乏,对患者和医疗体系构成了严重威胁。噬菌体编码的肽聚糖水解酶(内溶素)代表了一类有前途的新型抗菌药物。在过去的二十年中,对这些酶的研究已经从基础的体外特性描述发展到了复杂的蛋白质工程方法,包括先进的临床前和临床试验。近年来,越来越具体的动物模型显示了内溶素对各种不同器官和组织细菌感染的疗效。尽管取得了这些进展,但内溶素系统应用仍存在一些挑战需要解决。这些挑战包括免疫原性、循环半衰期以及细胞和组织特异性靶向和穿透特性。