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A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment

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Plasmid Acquisition Alters Vancomycin Susceptibility in Clostridioides difficile.

Meng Pu¹, Janice M Cho¹, Scott A Cunningham²

¹Division of Gastroenterology and Hepatology, Department of Medicine, Rochester, Minnesota.

Gastroenterology

|November 16, 2020

Summary

A newly identified plasmid may explain why some Clostridioides difficile infections (CDI) resist vancomycin treatment. This transferable plasmid reduced vancomycin susceptibility in lab tests and worsened disease in mice, suggesting a new mechanism for treatment failure.

Keywords:

Amidase Antimicrobial Resistance Cell Wall Peptidoglycan Gram Positive

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Area of Science:

Microbiology
Infectious Diseases
Genetics

Background:

Clostridioides difficile infections (CDI) are increasing, with rising resistance to current treatments like vancomycin.
The changing biology of C. difficile may contribute to treatment evasion and recurring infections.

Purpose of the Study:

To investigate a potential plasmid-mediated mechanism for decreased vancomycin susceptibility in C. difficile.
To explore the role of plasmid transfer in vancomycin treatment failure.

Main Methods:

Identification of a transferable plasmid in a vancomycin-resistant C. difficile strain.
In vitro experiments transferring the plasmid to a vancomycin-susceptible strain.
Evaluation of disease severity in a humanized mouse model post-plasmid transfer.

Main Results:

A broad host range transferable plasmid was identified in a C. difficile strain with poor vancomycin response.
Plasmid transfer decreased vancomycin susceptibility in vitro.
Transferred plasmid led to more severe disease in a humanized mouse model.

Conclusions:

Plasmid acquisition in the gastrointestinal tract is a potential mechanism for vancomycin treatment failure in CDI.
Further research is needed to elucidate the specific plasmid genes and mechanisms affecting vancomycin susceptibility.