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Stringent Response in E. coli01:23

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Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
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The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
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Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
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The trp operon in Escherichia coli exemplifies a repressible operon. It regulates the synthesis of tryptophan through repressor-mediated transcriptional control and attenuation. This dual regulatory mechanism ensures tryptophan biosynthesis occurs only when needed, conserving cellular resources.Structure of the trp OperonThe trp operon consists of five structural genes (trpE, trpD, trpC, trpB, and trpA) that encode enzymes for tryptophan biosynthesis. These genes are transcribed as a single...
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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
PubMed
Summary
This summary is machine-generated.

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.

Keywords:
antibiotic resistanceevolutionfluoroquinolonesgeneral stress responsemutagenic break repairmutationsppGppreactive oxygen speciesstress-induced mutagenesisstringent response

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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.