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Updated: Jun 29, 2025
Population and Single-Cell Analysis of Antibiotic Persistence in Escherichia coli
Published on: March 24, 2023
TisB protein is the single molecular determinant underlying multiple downstream effects of ofloxacin in Escherichia
Julien Cayron1, Thierry Oms1, Tatjana Schlechtweg1
1Bacterial Genetics and Physiology, Faculté des Sciences, Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium.
Abstract:
Bactericidal antibiotics can cause metabolic perturbations that contribute to antibiotic-induced lethality. The molecular mechanism underlying these downstream effects remains unknown. Here, we show that ofloxacin, a fluoroquinolone that poisons DNA gyrase, induces a cascade of metabolic changes that are dependent on an active SOS response. We identified the SOS-regulated TisB protein as the unique molecular determinant responsible for cytoplasmic condensation, proton motive force dissipation, loss of pH homeostasis, and H2O2 accumulation in Escherichia coli cells treated with high doses of ofloxacin. However, TisB is not required for high doses of ofloxacin to interfere with the function of DNA gyrase or the resulting rapid inhibition of DNA replication and lethal DNA damage. Overall, the study sheds light on the molecular mechanisms by which ofloxacin affects bacterial cells and highlights the role of the TisB protein in mediating these effects.
Insights
Bactericidal antibiotics like ofloxacin cause cell death through metabolic changes. The TisB protein is key to these effects, but not to the initial DNA damage caused by ofloxacin.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Bactericidal antibiotics can induce metabolic disruptions leading to cell death.
- The precise molecular mechanisms behind these antibiotic-induced metabolic changes are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of metabolic perturbations caused by ofloxacin.
- To identify the specific bacterial components mediating these downstream effects.
Main Methods:
- Utilized *Escherichia coli* as a model organism.
- Investigated the role of the SOS response and TisB protein in ofloxacin-induced metabolic changes.
- Assessed effects on cytoplasmic condensation, proton motive force, pH homeostasis, and hydrogen peroxide accumulation.
Main Results:
- Ofloxacin triggers a cascade of metabolic changes dependent on an active SOS response.
- The TisB protein was identified as the sole mediator of cytoplasmic condensation, proton motive force dissipation, loss of pH homeostasis, and H2O2 accumulation.
- TisB is not essential for ofloxacin's primary action on DNA gyrase or the subsequent DNA damage.
Conclusions:
- The study reveals TisB as a critical factor in ofloxacin's downstream metabolic effects.
- Highlights the distinct roles of TisB and DNA gyrase inhibition in ofloxacin-induced bacterial cell death.
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