Related Experiment Video
Updated: Aug 5, 2025
06:30
Using Microtiter Dish Radiolabeling for Multiple In Vivo Measurements Of Escherichia coli pppGpp Followed by Thin Layer Chromatography
Published on: June 4, 2019
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ppGpp and RNA-polymerase backtracking guide antibiotic-induced mutable gambler cells
Yin Zhai1, P J Minnick2, John P Pribis3
1Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Molecular Cell
|March 25, 2023
Summary
Antibiotic resistance arises from mutations. Researchers found that the stringent starvation response in E. coli, activated by ciprofloxacin, creates mutable cells and reveals new drug targets to combat resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Antibiotic resistance is a significant global health concern, frequently driven by genetic mutations.
- Antibiotics can promote mutations through stress responses, highlighting potential targets for intervention.
- The precise roles of stress responses in mutagenesis remain largely unclear.
Purpose of the Study:
- To identify stress responses involved in fluoroquinolone-antibiotic-induced mutagenesis in Escherichia coli.
- To elucidate the mechanisms by which antibiotic stress leads to increased mutation rates.
- To discover novel targets for drugs that can inhibit antibiotic resistance evolution.
Main Methods:
- Investigated the role of the stringent starvation response in ciprofloxacin-induced mutagenesis.
- Utilized molecular biology techniques to study the interaction of ppGpp with RNA polymerase (RNAP).
- Analyzed the activation of DNA-damage response and sigma-S (σS) response pathways.
Main Results:
- Identified the stringent starvation response as crucial for ciprofloxacin-induced mutagenesis.
- Discovered that ppGpp binding to RNAP at two distinct sites generates a mutable subpopulation of cells.
- Showed that ppGpp-site-1-RNAP activates the DNA-damage response, while ppGpp-site-2-RNAP induces σS-response activity.
- Demonstrated that these stress responses are essential for mutagenic DNA-break repair.
Conclusions:
- The stringent starvation response and RNAP regulation play a critical role in ciprofloxacin-induced mutagenesis.
- RNA polymerase (RNAP) appears to regulate DNA-break repair in transcribed regions.
- These findings identify potential targets for developing drugs to overcome antibiotic resistance.
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