title: Engineering bacterial thiosulfate and tetrathionate sensors for detecting gut inflammation.
abstract: There is a groundswell of interest in using genetically engineered sensor bacteria to study gut microbiota pathways, and diagnose or treat associated diseases. Here, we computationally identify the first biological thiosulfate sensor and an improved tetrathionate sensor, both two-component systems from marineShewanellaspecies, and validate them in laboratoryEscherichia coliThen, we port these sensors into a gut-adapted probioticE. colistrain, and develop a method based upon oral gavage and flow cytometry of colon and fecal samples to demonstrate that colon inflammation (colitis) activates the thiosulfate sensor in mice harboring native gut microbiota. Our thiosulfate sensor may have applications in bacterial diagnostics or therapeutics. Finally, our approach can be replicated for a wide range of bacterial sensors and should thus enable a new class of minimally invasive studies of gut microbiota pathways.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Kristina N-M
authors.identifier: 0000-0002-7464-5341
authors.initials: KN
authors.lastname: Daeffler
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Galley
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Ravi U
authors.initials: RU
authors.lastname: Sheth
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Ortiz-Velez
authors.affiliation: Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
authors.forename: Christopher O
authors.initials: CO
authors.lastname: Bibb
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Noah F
authors.identifier: 0000-0002-5934-2852
authors.initials: NF
authors.lastname: Shroyer
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Britton
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA jeff.tabor@rice.edu.|Department of Biosciences, Rice University, Houston, TX, USA.
authors.forename: Jeffrey J
authors.identifier: 0000-0001-7316-0361
authors.initials: JJ
authors.lastname: Tabor
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D015374:Biosensing Techniques; D003092:Colitis / Q000139:chemically induced / Q000175:diagnosis / Q000382:microbiology*; D003106:Colon / Q000382:microbiology; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D051379:Mice; D020592:Shewanella / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000009:adverse effects; D049490:Systems Biology / Q000379:methods; D013776:Tetrathionic Acid / Q000032:analysis*; D013885:Thiosulfates / Q000032:analysis*
chemical_list: D001426:Bacterial Proteins; D013885:Thiosulfates; D012967:Sodium Dodecyl Sulfate; D013776:Tetrathionic Acid
keywords: diagnostic bacteria; gut inflammation; tetrathionate; thiosulfate; two‐component system