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Toxin A-Predominant Pathogenic Clostridioides difficile: A Novel Clinical Phenotype
Qianyun Lin1,2, Nira R Pollock3,4, Alice Banz5
1Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Summary
New Clostridioides difficile strains producing high toxin A and low toxin B were discovered. This finding is significant for understanding C. difficile infection (CDI) and developing diagnostics and treatments.
Area of Science:
- Microbiology
- Infectious Diseases
- Gastroenterology
Background:
- Most Clostridioides difficile strains produce both toxin A and B.
- Toxin A-negative, toxin B-positive strains also cause disease.
- Pathogenic C. difficile isolates producing high toxin A and low/undetectable toxin B were identified.
Purpose of the Study:
- To identify and characterize C. difficile strains with predominant toxin A production.
- To evaluate the clinical significance and pathogenic potential of these strains.
- To understand the implications for C. difficile infection (CDI) diagnosis, treatment, and vaccine development.
Main Methods:
- Ultrasensitive, quantitative immunoassay to measure toxins A and B in stool samples.
- Culture of C. difficile isolates to assess in vitro toxin production.
- In vivo mouse model to evaluate disease phenotypes.
- Ribotyping for strain diversity assessment.
Main Results:
- 5.6% of samples showed detectable toxin A but undetectable toxin B (median TcdA:B ratio 17.93).
- In vitro cultures showed toxin A significantly exceeded toxin B (median ratio 26).
- Toxin A-predominant isolates caused diarrhea and lethal disease in mice; strain diversity was observed.
Conclusions:
- Discovery of clinical pathogenic C. difficile strains with high toxin A and minimal/no toxin B.
- This toxin profile is not rare (>5% of isolates) and is consistent in vitro and in vivo.
- Highlights toxin A's significance in CDI pathogenesis and impacts diagnostic, therapeutic, and vaccine strategies.
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