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Updated: Jul 13, 2026
09:47
Imaging of mtHyPer7, a Ratiometric Biosensor for Mitochondrial Peroxide, in Living Yeast Cells
Published on: June 2, 2023
Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor
Ashwani Kumar1, Jose C Toledo, Rakesh P Patel
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Summary
Mycobacterium tuberculosis senses host molecules using heme-containing sensor kinases DosS and DosT. These proteins detect oxygen, nitric oxide, and carbon monoxide to control bacterial gene expression and persistence.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Understanding oxidative stress responses in Mycobacterium tuberculosis (Mtb) is crucial for controlling infections.
- The dormancy/NO (Dos) regulon, regulated by DosS, DosT, and DosR, controls Mtb's genetic response to hypoxia and nitric oxide (NO).
- The specific ligands and sensing mechanisms of DosS and DosT remained largely unknown.
Purpose of the Study:
- To elucidate the regulatory ligands and signal sensing mechanisms of the Mtb sensor kinases DosS and DosT.
- To determine how these sensor kinases control the Dos regulon in response to host-derived molecules.
- To identify novel dormancy signals that influence Mtb survival.
Main Methods:
- Electron Paramagnetic Resonance (EPR) spectroscopy.
- UV-visible spectroscopy.
- Autokinase activity assays.
Main Results:
- Both DosS and DosT bind heme as a prosthetic group.
- DosS exists in a rapidly autooxidized met (Fe3+) form, while DosT is in the O2-bound (oxy) form.
- Oxygen (O2), nitric oxide (NO), and carbon monoxide (CO) were identified as ligands for DosS and DosT.
- The heme iron's oxidation or ligation state modulates DosS and DosT autokinase activity, with ferrous DosS and deoxy DosT exhibiting higher activity.
- Carbon monoxide (CO) was identified as a novel inducer of the Mtb Dos regulon.
Conclusions:
- DosS functions as a redox sensor, and DosT functions as a hypoxia sensor.
- O2, NO, and CO act as modulatory ligands for DosS and DosT, finely tuning Mtb's response.
- Mtb employs sophisticated sensing strategies for O2, NO, and CO, contributing to bacterial persistence.
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