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Updated: Jun 21, 2026

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
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Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291

Published on: December 10, 2016

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Clostridioides difficile MreE (PBP2) variants facilitate clinical disease during cephalosporin exposures

Jay Noboru Worley1,2, Nicholas D Benedetto1, Mary Delaney1,3

  • 1Massachusetts Host-Microbiome Center, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Medrxiv : the Preprint Server for Health Sciences
|November 14, 2023
PubMed

Insights

Cephalosporins drive healthcare-associated Clostridioides difficile infections (CDI). Gene variants in mreE penicillin-binding protein 2 (PBP2) confer cephalosporin resistance, promoting CDI development and spread.

Area of Science:

  • Microbiology
  • Genomics
  • Epidemiology

Background:

  • Healthcare-associated Clostridioides difficile infections (CDI) are frequently linked to cephalosporin antibiotic use.
  • Understanding the genetic basis of cephalosporin resistance in C. difficile is crucial for infection control.

Approach:

  • Genomic-epidemiologic analysis of 306 C. difficile isolates from hospital surveillance.
  • Investigated resistance to ceftriaxone and identified specific gene variants.
  • Functional studies involving gene transfer into susceptible C. difficile strains and mouse models.

Key Points:

  • 26% of isolates showed high-level resistance to third-generation cephalosporins (ceftriaxone), associated with prior patient cephalosporin exposure.
  • Identified variants in the mreE penicillin-binding protein 2 (PBP2) gene linked to resistance across multiple beta-lactam classes.
  • Transferred mreE variants conferred cephalosporin resistance and disease-causing potential in a mouse model.

Conclusions:

  • Cephalosporins and specific mreE variants are confirmed drivers of CDI.
  • These findings provide genetic targets for detecting cephalosporin resistance in clinical C. difficile isolates.

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