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Related Concept Videos

Stringent Response in E. coli01:23

Stringent Response in E. coli

49
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
49

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Related Experiment Video

Updated: Sep 3, 2025

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
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Low-toxin Clostridioides difficile RT027 strains exhibit robust virulence.

Farhan Anwar1, Bryan Angelo P Roxas1, Kareem W Shehab2

  • 1School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, USA.

Emerging Microbes & Infections
|July 26, 2022
PubMed
Summary

Toxigenic Clostridioides difficile strains can be missed by toxin tests, challenging current diagnostics. Low-toxin strains show significant virulence, suggesting a need to re-evaluate diagnostic strategies for C. difficile infection.

Keywords:
Clostridioides difficileRT027low-toxintoxinvirulence

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Area of Science:

  • Microbiology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Clostridioides difficile infection (CDI) is a major healthcare-associated infection.
  • Current diagnostic methods, often multi-step algorithms using enzyme immunosorbent analysis (EIA) for toxins, lack universal consensus.
  • EIA toxin-negative (Tox-) results are presumed to indicate less severe disease.

Purpose of the Study:

  • To characterize toxigenic Clostridioides difficile strains from EIA Tox- (discrepant) results.
  • To evaluate the virulence of these low-toxin strains.
  • To assess the limitations of current CDI diagnostic protocols.

Main Methods:

  • Isolation and ribotyping of C. difficile strains from patient stool specimens.
  • Toxin, genome, and proteome evaluations.
  • Virulence assessment in cell cultures and animal models (hamsters, mice).

Main Results:

  • 31% of C. difficile-positive specimens showed discrepant EIA Tox- results.
  • Low-toxin RT027 strains (LT-027) were cytotoxic and exhibited significant lethality in hamsters.
  • LT-027 strains demonstrated heightened colonization and persistence in mice, with unique genomic and proteomic profiles.

Conclusions:

  • Low-toxin Clostridioides difficile strains possess robust virulence.
  • EIA toxin-negative results may not reliably exclude significant disease.
  • Current diagnostic protocols for CDI may have limitations that need reconsideration.