Center for Bacterial Pathogenesis, Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, MA 02115, USA; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Center for Bacterial Pathogenesis, Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, MA 02115, USA; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Trends Pharmacol Sci. 2022 Sep;43(9):772-786. doi: 10.1016/j.tips.2022.02.002. Epub 2022 Feb 26.
Engineered microbes are rapidly being developed for the delivery of therapeutic modalities to sites of disease. Escherichia coli Nissle 1917 (EcN), a genetically tractable probiotic with a well-established human safety record, is emerging as a favored chassis. Here, we summarize the latest progress in rationally engineered variants of EcN for the treatment of infectious diseases, metabolic disorders, and inflammatory bowel diseases (IBDs) when administered orally, as well as cancers when injected directly into tumors or the systemic circulation. We also discuss emerging studies that raise potential safety concerns regarding these EcN-based strains as therapeutics due to their secretion of a genotoxic colibactin that can promote the formation of DNA double-stranded breaks in mammalian DNA.
工程菌正在迅速被开发出来，用于将治疗方式递送到疾病部位。大肠杆菌 Nissle 1917（EcN）是一种具有良好的人体安全性记录的可遗传益生菌，正逐渐成为一种受欢迎的底盘。在这里，我们总结了最近在理性设计的 EcN 变体方面的进展，这些变体可用于治疗感染性疾病、代谢紊乱和炎症性肠病（IBD），当口服给药时，以及当直接注射到肿瘤或全身循环中时用于治疗癌症。我们还讨论了一些新的研究，这些研究由于其分泌的一种遗传毒性的大肠菌素，可能会导致哺乳动物 DNA 中双链 DNA 断裂的形成，从而对这些基于 EcN 的菌株作为治疗剂的潜在安全性提出了担忧。
