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Updated: May 5, 2026
10:41
Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
Published on: January 3, 2012
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Single-cell analysis reveals critical toxin/antitoxin ratio triggering persister resuscitation
Lina Wu1, Qingqing Wang2, Xinyi Hong2
1Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, China. alina1222@xmu.edu.cn.
Molecular Systems Biology
|January 3, 2026
Summary
Persister bacteria, tolerant to antibiotics, form deeper dormant states when exposed to low antibiotic doses. High toxin/antitoxin ratios are critical for persister survival and resuscitation.
Area of Science:
- Microbiology
- Bacterial Physiology
- Antimicrobial Resistance
Background:
- Persisters are transient, antibiotic-tolerant bacterial subpopulations contributing to treatment failure.
- Mechanisms of persister formation and resuscitation are not fully understood.
- Understanding persister dynamics is crucial for developing effective antimicrobial strategies.
Purpose of the Study:
- To investigate the molecular mechanisms of bacterial persister formation and resuscitation.
- To quantify toxin-antitoxin levels and monitor cell wall growth in single persister cells.
- To elucidate the role of the toxin/antitoxin (T/A) ratio in persister cell survival and resuscitation.
Main Methods:
- Development of nano-flow cytometry (nFCM) for single-cell analysis.
- Quantification of RelE (toxin) and RelB (antitoxin) levels.
- Monitoring of cell wall growth dynamics.
- Proteomic profiling of persister cells.
Main Results:
- Bacteria elevate the T/A ratio via two expression modalities to survive antibiotic challenge, with T/A=1.0 as a critical threshold.
- Subinhibitory antibiotic concentrations induce deeper dormancy with elevated T/A ratios.
- Resuscitation involves a triphasic detoxification process, reducing the T/A ratio to a proliferation-permissive level.
- Persisters with high RelE show increased transmembrane transporter levels associated with stress response and drug efflux.
Conclusions:
- The T/A ratio is a critical regulator of bacterial persister states.
- Maximizing therapeutic antibiotic concentrations is essential to prevent deeper dormancy.
- High-throughput, single-cell analysis is vital for understanding persister heterogeneity and developing targeted therapies.
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