Congrats to Ilia Gelfat, Anton Kan, Siva Emani, and Pichet (Bom) Praveschotinunt on their new publication out in ACS Synthetic Biology! It describes the engineering of a plasmid system that is compatible with a probiotic E. coli strain (Nissle 1917) and is retained even as the bacterium traverses the mammalian gastrointestinal tract. They show that this engineered plasmid system is easily modified to express and secrete heterologous proteins, does not require antibiotic selection, and that the genes of interest are produced in response to a temperature-sensitive promoter, so they are only “on” inside the host, but can remain “off” when cultured at lower temperatures in the lab. Remarkably, the plasmids remain associated with the strain even though they encode for proteins that are very stressful for the bacteria to produce and the bacteria must also compete with the native microbiota in the gut! We hope we and others can use this tool to accelerate the field of living therapeutics.