期刊
CELL
卷 169, 期 3, 页码 538-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2017.03.041
关键词
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资金
- Stanford's Discovery Innovation Fund in Basic Biomedical Sciences
- National Institutes of Health NIDDK [R01-DK101674, R01-DK085025]
- NSF [DGE-114747]
- Crohn's and Colitis Foundation of America research fellowship award
- NIH training grants [5T32AI007502-18, 5T32AI007328-25]
Applying synthetic biology to engineer gut-resident microbes provides new avenues to investigate microbe-host interactions, perform diagnostics, and deliver therapeutics. Here, we describe a platform for engineering Bacteroides, the most abundant genus in the Western microbiota, which includes a process for high-throughput strain modification. We have identified a novel phage promoter and translational tuning strategy and achieved an unprecedented level of expression that enables imaging of fluorescent-protein-expressing Bacteroides stably colonizing the mouse gut. A detailed characterization of the phage promoter has provided a set of constitutive promoters that span over four logs of strength without detectable fitness burden within the gut over 14 days. These promoters function predictably over a 1,000,000-fold expression range in phylogenetically diverse Bacteroides species. With these promoters, unique fluorescent signatures were encoded to allow differentiation of six species within the gut. Fluorescent protein-based differentiation of isogenic strains revealed that priority of gut colonization determines colonic crypt occupancy.
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