Functional interplay between (p)ppGpp and RNAP in Acinetobacter baumannii.
Anthony Perrier1, Aurélie Budin-Verneuil2, Régis Hallez1
1Bacterial Cell cycle & Development (BCcD), Biology of Microorganisms Research Unit (URBM), Namur Research Institute for Life Science (NARILIS), University of Namur, Namur, Belgium.
Plos Pathogens
|December 18, 2025
Summary
The stringent response (p)ppGpp is vital for Acinetobacter baumannii survival. This study reveals how (p)ppGpp impacts motility, stress tolerance, and virulence, highlighting its role in pathogenic bacteria.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- The stringent response, mediated by guanosine tetraphosphate ((p)ppGpp), is crucial for bacterial survival under stress.
- Mechanisms of (p)ppGpp-mediated survival in pathogenic bacteria, particularly Acinetobacter baumannii, remain largely uncharacterized.
Purpose of the Study:
- To characterize (p)ppGpp metabolism and its physiological consequences in the opportunistic pathogen Acinetobacter baumannii.
- To identify genetic factors, specifically RNA polymerase (RNAP) mutations, that modulate (p)ppGpp-dependent phenotypes.
Main Methods:
- Induction of (p)ppGpp production under iron starvation and polymyxin exposure.
- Phenotypic analysis of A. baumannii mutants lacking (p)ppGpp, including motility, catalase activity, and survival assays.
- Motility suppressor screens and deep sequencing to identify mutations in rpoB and rpoC.
- Transcriptomic analysis to assess the impact of (p)ppGpp on gene expression.
Main Results:
- (p)ppGpp production is induced by iron starvation and polymyxin exposure in A. baumannii.
- Absence of (p)ppGpp leads to increased motility, decreased catalase activity, poor nutrient starvation survival, desiccation sensitivity, and attenuated virulence in a Galleria mellonella model.
- Stringent mutations in rpoB and rpoC were identified as suppressors of (p)ppGpp-dependent phenotypes.
- (p)ppGpp significantly alters the transcriptional landscape, inducing stress-related genes like catalase and hydrophilins crucial for desiccation tolerance.
Conclusions:
- The (p)ppGpp-dependent stringent response is essential for Acinetobacter baumannii survival and virulence.
- A functional interplay exists between (p)ppGpp and RNAP in mediating bacterial adaptation to environmental and host-associated stresses.
- This study provides insights into the molecular mechanisms underlying bacterial stress survival and identifies potential targets for therapeutic intervention.
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