Engineering bacterial thiosulfate and tetrathionate sensors for detecting gut inflammation

Mol Syst Biol. 2017 Apr 3;13(4):923. doi: 10.15252/msb.20167416.

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 marine Shewanella species, and validate them in laboratory Escherichia coli Then, we port these sensors into a gut-adapted probiotic E. coli strain, 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.

Keywords: diagnostic bacteria; gut inflammation; tetrathionate; thiosulfate; two‐component system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Biosensing Techniques
  • Colitis / chemically induced
  • Colitis / diagnosis
  • Colitis / microbiology*
  • Colon / microbiology
  • Disease Models, Animal
  • Feces / microbiology
  • Gastrointestinal Microbiome
  • Mice
  • Shewanella / metabolism
  • Sodium Dodecyl Sulfate / adverse effects
  • Systems Biology / methods
  • Tetrathionic Acid / analysis*
  • Thiosulfates / analysis*

Substances

  • Bacterial Proteins
  • Thiosulfates
  • Sodium Dodecyl Sulfate
  • Tetrathionic Acid