Clostridioides difficile Binary Toxin Binding Component Increases Virulence in a Hamster Model

Simpson, Morgan; Bilverstone, Terry; Leslie, Jhansi; Donlan, Alexandra; Uddin, Md Jashim; Petri, William A; Marin, Natasha; Kuehne, Sarah; Minton, Nigel P and Petri, William A (2023). Clostridioides difficile Binary Toxin Binding Component Increases Virulence in a Hamster Model. Open Forum Infectious Diseases, 10(3)

DOI: https://doi.org/10.1093/ofid/ofad040

Abstract

Background
Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. Although the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection.
Methods
To determine the contribution of the separate components of CDT during infection, we developed strains of C difficile expressing either CDTa or CDTb individually. We then infected both mice and hamsters with these novel mutant strains and monitored them for development of severe illness.
Results
Although expression of CDTb without CDTa did not induce significant disease in a mouse model of C difficile infection, we found that complementation of a CDT-deficient C difficile strain with CDTb alone restored virulence in a hamster model of C difficile infection.
Conclusions
Overall, this study demonstrates that the binding component of C difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection.

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