Related Experiment Video

Updated: Feb 4, 2026

Using Microtiter Dish Radiolabeling for Multiple In Vivo Measurements Of Escherichia coli pppGpp Followed by Thin Layer Chromatography
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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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(p)ppGpp mediates persister formation in Escherichia coli during glucose to fatty acid shift

Ruixue Zhang1, Zhengyang Xiao1, Neha Namburi1

  • 1Department of Energy, Environmental & Chemical Engineering, Washington University in St. Louis, St. Louis, MO, United States.

Frontiers in Microbiology
|February 2, 2026
PubMed

Insights

Fatty acid shifts dramatically increase bacterial persister cells by raising (p)ppGpp levels. Targeting these metabolic pathways could reduce antibiotic resistance and recurrent infections.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Bacterial persistence is a key factor in antibiotic treatment failure and recurrent infections.
  • The metabolic triggers for persister cell formation are not well understood.
  • Investigating nutrient shifts in *Escherichia coli* can elucidate mechanisms of persistence.

Purpose of the Study:

  • To investigate the role of different carbon sources in *Escherichia coli* persister formation.
  • To determine the metabolic cues, particularly (p)ppGpp, that influence persister development after nutrient downshifts.
  • To identify potential therapeutic targets for reducing bacterial persistence.

Main Methods:

  • Comparative analysis of *Escherichia coli* persistence after shifting from glucose to various carbon sources (fatty acids vs. gluconeogenic carbons).
  • Quantification of guanosine tetra- and penta-phosphate [(p)ppGpp] levels using RNA-based biosensors and HPLC.
  • Genetic manipulation (overexpression of acyl-ACP synthase and PlsB) to assess its impact on (p)ppGpp levels and persistence.
  • Metabolic analysis using 13C isotope tracing and metabolomics to understand carbon flux in persister cells.

Main Results:

  • Shifting *E. coli* from glucose to fatty acids induced significantly higher persister levels compared to shifts to gluconeogenic carbons.
  • Elevated (p)ppGpp levels were observed during prolonged carbon starvation after glucose-to-fatty acid shifts, correlating with increased persistence.
  • Reducing lag phase duration or manipulating (p)ppGpp synthesis/inhibition pathways decreased persister formation.
  • Persister cells demonstrated metabolic adaptability, rerouting carbon flux into gluconeogenesis and the pentose phosphate pathway.

Conclusions:

  • The (p)ppGpp signaling molecule plays a crucial role in nutrient shift-induced persister formation in *E. coli*.
  • Metabolic adaptation, including flux into gluconeogenesis and the pentose phosphate pathway, supports persister cell survival.
  • Targeting (p)ppGpp-related pathways and metabolic remodeling offers potential strategies to combat antibiotic resistance and recurrent infections.
Keywords:
(p)ppGppbacterial persistencenutrient shiftsingle-cell imagingstress response

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