Bacterial variability in the mammalian gut captured by a single-cell synthetic oscillator

David T. Riglar, David L. Richmond, Laurent Potvin-Trottier, Andrew A. Verdegaal, Alexander D. Naydich, Somenath Bakshi, Emanuele Leoncini, Lorena G. Lyon, Johan Paulsson and Pamela A. Silver ()
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David T. Riglar: Harvard Medical School
David L. Richmond: Harvard Medical School
Laurent Potvin-Trottier: Harvard Medical School
Andrew A. Verdegaal: Harvard Medical School
Alexander D. Naydich: Harvard Medical School
Somenath Bakshi: Harvard Medical School
Emanuele Leoncini: Harvard Medical School
Lorena G. Lyon: Harvard Medical School
Johan Paulsson: Harvard Medical School
Pamela A. Silver: Harvard Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Synthetic gene oscillators have the potential to control timed functions and periodic gene expression in engineered cells. Such oscillators have been refined in bacteria in vitro, however, these systems have lacked the robustness and precision necessary for applications in complex in vivo environments, such as the mammalian gut. Here, we demonstrate the implementation of a synthetic oscillator capable of keeping robust time in the mouse gut over periods of days. The oscillations provide a marker of bacterial growth at a single-cell level enabling quantification of bacterial dynamics in response to inflammation and underlying variations in the gut microbiota. Our work directly detects increased bacterial growth heterogeneity during disease and differences between spatial niches in the gut, demonstrating the deployment of a precise engineered genetic oscillator in real-life settings.

Date: 2019
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DOI: 10.1038/s41467-019-12638-z

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