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Ligand Binding and Linkage

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A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment
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Published on: May 25, 2017

Naturally Occurring CodY Variants Alter Ligand Binding, DNA Target Affinity, and Virulence in Clostridioides

Md Kamrul Hasan1, Sourav Roy2, Revathi Govind1

  • 1Division of Biology, Kansas State University, Manhattan, Kansas, USA.

Molecular Microbiology
|June 3, 2026
PubMed
Summary

Altering the global regulator CodY in Clostridioides difficile affects its ability to control toxin production. These genetic changes increase virulence, highlighting CodY

Keywords:
Clostridioides difficileCodYvirulence

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Identifying the Binding Proteins of Small Ligands with the Differential Radial Capillary Action of Ligand Assay (DRaCALA)
09:26

Identifying the Binding Proteins of Small Ligands with the Differential Radial Capillary Action of Ligand Assay (DRaCALA)

Published on: March 19, 2021

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Clostridioides difficile is a significant cause of hospital-acquired infections, leading to antibiotic-associated diarrhea and colitis.
  • CodY is a global regulator in Gram-positive pathogens, controlling metabolism and virulence by sensing amino acids and GTP.
  • In C. difficile, CodY normally represses toxin production and influences c-di-GMP levels.

Purpose of the Study:

  • To investigate the impact of naturally occurring CodY variants on C. difficile virulence.
  • To characterize how specific amino acid substitutions affect CodY's ligand binding and regulatory functions.
  • To assess the role of CodY variants in C. difficile pathogenicity.

Main Methods:

  • Characterization of two CodY variants (CodY(Y146N) and CodY(V58A)) with substitutions near ligand-binding sites.
  • Assessing GTP and leucine binding affinities for CodY variants.
  • Evaluating ligand-dependent binding to the tcdR promoter and measuring virulence gene expression.
  • Testing the pathogenicity of variant-producing strains in a hamster infection model.

Main Results:

  • CodY(Y146N) showed compromised GTP binding and enhanced leucine binding; CodY(V58A) had reduced leucine binding.
  • Both variants displayed reduced binding to the tcdR promoter and were less effective at repressing toxin production.
  • Strains producing either CodY variant showed elevated expression of virulence genes (tcdR, pdcB) and increased virulence in hamsters.

Conclusions:

  • Single amino acid substitutions in CodY can significantly alter its ligand-binding properties and promoter interactions.
  • These alterations can disrupt the regulatory network, leading to enhanced expression of virulence factors.
  • Modified CodY variants can increase the pathogenic potential of Clostridioides difficile.