ATP-Dependent Dynamic Protein Aggregation Regulates Bacterial Dormancy Depth Critical for Antibiotic Tolerance
Yingying Pu1, Yingxing Li1, Xin Jin1
1Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
Molecular Cell
|November 26, 2018
Summary
Bacterial cells exhibit varying dormancy depths, influencing their regrowth after antibiotic exposure. Protein aggresomes indicate dormancy depth and must be cleared for resuscitation, impacting antibiotic tolerance strategies.
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Bacterial cell dormancy is a survival strategy against antibiotics.
- Antibiotic tolerance and regrowth dynamics at the single-cell level are not fully understood.
Purpose of the Study:
- To investigate the factors regulating bacterial dormancy depth and regrowth after antibiotic treatment.
- To identify key indicators and mechanisms involved in bacterial cell resuscitation.
Main Methods:
- Single-cell monitoring of bacterial antibiotic tolerance and regrowth.
- Analysis of protein aggresome formation and its correlation with dormancy.
- Investigation of ATP levels and DnaK-ClpB machinery recruitment in cell resuscitation.
Main Results:
- Individual bacterial cells display diverse dormancy depths, affecting resuscitation lag times.
- Protein aggresomes, promoted by low ATP, serve as indicators of bacterial dormancy depth.
- Clearance of protein aggresomes and functional DnaK-ClpB recruitment are crucial for bacterial regrowth.
Conclusions:
- Bacterial regrowth after antibiotic exposure is regulated by dormancy depth and proteostasis recovery.
- Protein aggresome dynamics and ATP-dependent disaggregation machinery are key targets for therapeutic strategies against antibiotic tolerance.
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