Related Experiment Video

Updated: Mar 6, 2026

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa
11:31

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa

Published on: June 30, 2016

9.2K

Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion

Ronan R McCarthy1, Maria J Mazon-Moya2, Joana A Moscoso1

  • 1MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

Nature Microbiology
|March 7, 2017
PubMed

Insights

Researchers discovered WarA, a protein that binds cyclic-di-GMP, influencing Pseudomonas aeruginosa biofilm formation and immune evasion. This finding reveals a new mechanism in bacterial pathogenesis.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Pseudomonas aeruginosa is a Gram-negative bacterium causing acute and chronic infections.
  • The cyclic-di-GMP second messenger regulates the transition from motility to biofilm formation, crucial for infections like cystic fibrosis.
  • SadC, a diguanylate cyclase, is involved in this adaptive transition.

Purpose of the Study:

  • To identify novel partners of SadC involved in Pseudomonas aeruginosa pathogenesis.
  • To elucidate the function of WarA and its associated protein WarB.
  • To investigate the role of WarA in lipopolysaccharide (LPS) O antigen regulation and host immune evasion.

Main Methods:

  • Protein interaction studies to identify SadC partners.
  • Biochemical assays to characterize WarA's methyltransferase activity and cyclic-di-GMP binding.
  • Structural analysis comparing WarA/WarB to known regulators.
  • Zebrafish infection model to assess WarA's role in virulence and host immune evasion.

Main Results:

  • WarA was identified as a novel partner of SadC.
  • WarA functions as a cyclic-di-GMP-potentiated methyltransferase, with WarB as a putative kinase.
  • WarA/WarB complex shares structural similarities with E. coli LPS regulator WbdD.
  • WarA influences P. aeruginosa O antigen distribution and interacts with LPS biogenesis machinery.
  • WarA contributes to P. aeruginosa's ability to evade host immune detection in a zebrafish model.

Conclusions:

  • WarA is a novel effector protein regulated by cyclic-di-GMP, impacting P. aeruginosa LPS O antigen.
  • The WarA/WarB complex represents a new regulatory system in P. aeruginosa virulence.
  • WarA plays a significant role in bacterial immune evasion, highlighting a potential therapeutic target.

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