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Emerging Clostridioides difficile ribotypes have divergent metabolic phenotypes.

Firas S Midani1,2, Heather A Danhof1,2, Nathanael Mathew1,2

  • 1Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA.

Biorxiv : the Preprint Server for Biology
|August 26, 2024
PubMed
Summary

Clostridioides difficile (C. difficile) is a versatile gut pathogen. This study reveals lineage-specific metabolic differences in C. difficile strains, impacting their adaptation and potential therapeutic strategies.

Keywords:
Clostridioides difficilecarbon metabolismgrowth modelingribotyping

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Area of Science:

  • Microbiology
  • Pathogen Metabolism
  • Genomics

Background:

  • Clostridioides difficile is a major cause of diarrheal infections.
  • Genetic diversity exists among C. difficile strains, with specific ribotypes dominating human infections.
  • Metabolic adaptations of epidemic C. difficile ribotypes remain largely unexplored.

Purpose of the Study:

  • To investigate carbon substrate utilization in a diverse collection of C. difficile clinical isolates.
  • To identify metabolic differences linked to specific ribotypes and phylogenetic lineages.
  • To understand the metabolic basis for the emergence and adaptation of C. difficile.

Main Methods:

  • Carbon substrate utilization profiling of 88 C. difficile clinical isolates.
  • Growth assays across 22 different ribotypes.
  • Phylogenetic analysis to correlate metabolic capabilities with genetic lineage.

Main Results:

  • C. difficile exhibits generalist metabolic capabilities, utilizing a wide range of carbon sources.
  • Metabolic phenotypes clustered by phylogenetic relationship, showing ribotype- and clade-specific differences.
  • Emerging lineages (ribotypes 023, 255) displayed divergent metabolic profiles.
  • The most evolutionarily distant clade (Clade 5) showed robust growth on simple sugars.

Conclusions:

  • C. difficile employs a generalist metabolic strategy, but with significant lineage-specific adaptations.
  • Metabolic diversity is crucial for understanding C. difficile evolution and pathogenesis.
  • Findings support the rational design of targeted therapeutic interventions by exploiting metabolic niches.