Bacteria can be engineered to function as diagnostics or therapeutics in the mammalian gut but commercial translation of these technologies has been hindered by the susceptibility of synthetic genetic circuits to mutation and unpredictable function during extended gut colonization. Here we report stable, engineered bacterial strains that maintain their function for 6 months in the mouse gut. We engineered a commensal murine Escherichia coli strain to detect tetrathionate, which is produced during inflammation. Using our engineered diagnostic strain, which retains memory of exposure in the gut for analysis by fecal testing, we detected tetrathionate in both infection-induced and genetic mouse models of inflammation over 6 months. The synthetic genetic circuits in the engineered strain were genetically stable and functioned as intended over time. The robust, durable performance of these strains confirms the potential of engineered bacteria as living diagnostics.
Cells organize and regulate their metabolism via membrane- or protein-bound organelles. In this way, incompatible processes can be spatially separated and controlled. In prokaryotes, protein-based compartments are used to sequester harmful reactions and store useful compounds. These protein compartments play key roles in various metabolic and ecological processes, ranging from iron homeostasis to carbon fixation. One of the newest types of protein organelle are encapsulin nanocompartments. They are able to encapsulate specific protein cargo and are proposed to be involved in redox-related processes. We identified more than 900 putative encapsulin systems in bacterial and archaeal genomes. Encapsulins can be found in fifteen bacterial and two archaeal phyla. Our analysis reveals one new capsid type and nine previously unknown cargo proteins targeted to the interior of encapsulins. We experimentally characterize three newly identified encapsulin systems and illustrate their probable involvement in iron mineralization, oxidative and nitrosative stress resistance and anaerobic ammonium oxidation, a process responsible for 30% of the nitrogen lost from the oceans.
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