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Abstract：
Gut bacteria are known to produce bacteriocins to inhibit the growth of other bacteria. Consequently, bacteriocins have attracted increased attention as potential microbiome-editing tools. In this study we examine the inhibitory spectrum of 75 class II bacteriocins against 48 representative gut microbiota species. The bacteriocins were heterologously expressed in Escherichia coli and evaluated in vitro, ex vivo and in vivo. In vitro assays revealed 22 bacteriocins to inhibit at least one species and showed selective inhibition patterns against species implicated in certain disorders and diseases. Three bacteriocins were selected for ex vivo assessment on mouse feces. Based on 16S rRNA sequencing of the cultivated feces we showed that the two bacteriocins: Actifencin (#13) and Bacteroidetocin A (#22) selectively inhibited the growth of Lactobacillus and Bacteroides, respectively. The probiotic: E. coli Nissle 1917 was engineered to express these two bacteriocins in mice. However, the selective inhibitory patterns found in the in vitro and ex vivo experiments could not be observed in vivo. Our study describes a methodology for heterologous high throughput bacteriocin expression and screening and elucidates the inhibitory patterns of class II bacteriocins on the gut microbiota.
摘要：
已知肠道细菌产生细菌素以抑制其他细菌的生长。因此,细菌素作为潜在的微生物组编辑工具已经引起了越来越多的关注。在这项研究中，我们检查了75种II类细菌素对48种代表性肠道微生物群的抑制谱。细菌素在大肠杆菌中异源表达，并在体外进行评估。离体和体内。体外测定显示22种细菌素抑制至少一种物种，并显示出对某些病症和疾病相关物种的选择性抑制模式。选择三种细菌素用于对小鼠粪便的离体评估。基于培养的粪便的16SrRNA测序，我们表明两种细菌素：Actifencin（＃13）和BacteroidotocinA（＃22）选择性地抑制乳杆菌和拟杆菌的生长，分别。益生菌:大肠杆菌Nissle1917被工程化以在小鼠中表达这两种细菌素。然而,在体内无法观察到在体外和离体实验中发现的选择性抑制模式。我们的研究描述了异源高通量细菌素表达和筛选的方法，并阐明了II类细菌素对肠道微生物群的抑制模式。
