Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA; Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA.
Cell Host Microbe. 2017 Sep 13;22(3):263-268.e4. doi: 10.1016/j.chom.2017.08.001. Epub 2017 Aug 31.
Synthetic biology has focused on engineering microbes to synthesize useful products or to serve as living diagnostics and therapeutics. Here we utilize a host-derived Escherichia coli strain engineered with a genetic toggle switch as a research tool to examine in vivo replicative states in a mouse model of chronic infection, and to compare in vivo and in vitro bacterial behavior. In contrast to the effect of antibiotics in vitro, we find that the fraction of actively dividing bacteria remains relatively high throughout the course of a chronic infection in vivo and increases in response to antibiotics. Moreover, the presence of non-dividing bacteria in vivo does not necessarily lead to an antibiotic-tolerant infection, in contrast to expectations from in vitro experiments. These results demonstrate the utility of engineered bacteria for querying pathogen behavior in vivo, and the importance of validating in vitro studies of antibiotic effects with in vivo models.
合成生物学专注于工程微生物来合成有用的产品，或用作活体诊断和治疗方法。在这里，我们利用一种经过基因 toggle 开关工程改造的宿主衍生大肠杆菌菌株作为研究工具，在慢性感染的小鼠模型中研究体内复制状态，并比较体内和体外细菌行为。与体外抗生素的作用相反，我们发现，在体内慢性感染过程中，活跃分裂的细菌比例相对较高，并对抗生素做出反应而增加。此外，与体外实验的预期相反，体内非分裂细菌的存在并不一定会导致抗生素耐受感染。这些结果表明，经过工程改造的细菌可用于在体内研究病原体行为，并且需要用体内模型验证体外抗生素作用研究的有效性。
