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High-throughput Screening of Chemical Compounds to Elucidate Their Effects on Bacterial Persistence
Published on: February 23, 2021
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ppGpp ribosome dimerization model for bacterial persister formation and resuscitation
1Department of Chemical Engineering, Pennsylvania State University, University Park, PA, 16802-4400, USA.
Biochemical and Biophysical Research Communications
|February 3, 2020
Summary
Bacteria develop dormant persister cells under stress, causing recurring infections. The new PRDP model shows guanosine tetraphosphate (ppGpp) inactivates ribosomes, forming these antibiotic-tolerant cells.
Area of Science:
- Microbiology
- Bacterial Physiology
- Infectious Diseases
Background:
- Bacterial stress responses can lead to dormant persister cells, contributing to chronic and recurrent infections like tuberculosis and Lyme disease.
- The precise mechanisms of persister cell formation remain poorly understood.
- Persister cells exhibit tolerance to antimicrobial treatments.
Purpose of the Study:
- To elucidate the mechanism of bacterial persister cell formation.
- To propose and validate the ppGpp ribosome dimerization persister (PRDP) model.
- To investigate the role of ribosome dimerization in bacterial persistence.
Main Methods:
- Development of the PRDP model involving guanosine tetraphosphate (ppGpp), ribosome modulation factor (RMF), hibernation promoting factor (Hpf), and ribosome-associated inhibitor (RaiA).
- Analysis of ribosome states (monomers vs. dimers) in persister cells.
- Genetic inactivation of RMF, Hpf, and RaiA to assess effects on persistence and resuscitation.
Main Results:
- Persister cells were found to contain a significant fraction of 100S (dimeric) ribosomes.
- Inactivation of RMF, Hpf, and RaiA led to reduced persistence and accelerated single-cell persister resuscitation.
- Guano sine tetraphosphate (ppGpp) did not directly affect single-cell persister resuscitation, but its role in ribosome inactivation was demonstrated.
Conclusions:
- The study establishes a direct link between ppGpp and bacterial persistence through ribosome inactivation.
- Ribosome dimerization is crucial for the formation and maintenance of persister cells.
- Understanding these mechanisms is vital for developing strategies against recurring bacterial infections.
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