Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation

• Published in: Nature biotechnology Vol. 35; no. 7; pp. 653 - 658
• Main Authors: Riglar, David T, Giessen, Tobias W, Baym, Michael, Kerns, S Jordan, Niederhuber, Matthew J, Bronson, Roderick T, Kotula, Jonathan W, Gerber, Georg K, Way, Jeffrey C, Silver, Pamela A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2017; Nature Publishing Group
• Subjects: 13/51; 14/10; 38/77; 42/41; 42/44; 42/70; 45/23; 631/154/140; 631/61/338/552; 64/110; 64/60; Agriculture; Animal models; Animals; Bacteria; Bioinformatics; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cell Survival; Circuits; Colonization; Diagnosis; Diagnostic systems; Diagnostics; E coli; Escherichia coli - genetics; Escherichia coli - isolation & purification; Escherichia coli - metabolism; Female; Gastroenteritis - diagnosis; Gastroenteritis - microbiology; Gastrointestinal Microbiome; Gastrointestinal tract; Genetic Engineering - methods; Genetically modified organisms; Health aspects; Inflammation; Intestines; letter; Life Sciences; Mammals; Mice; Mice, Inbred C57BL; Microbial colonies; Stomach; Tetrathionate; Tetrathionic Acid - metabolism; Tissue engineering
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.3879

An engineered commensal
E. coli
strain can function as a living diagnostic for a marker of inflammation in the murine gut for 200 days.
Bacteria can be engineered to function as diagnostics or therapeutics in the mammalian gut but commercial translation of technologies to accomplish this 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 durable performance of these strains confirms the potential of engineered bacteria as living diagnostics.