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MicrobiologybioRxiv

Clostridioides difficile binary toxin binding component (CDTb) increases virulence in a hamster model

M. Simpson, T. Bilverstone, J. L. Leslie, A. Donlan, M. J. Uddin, W. Petri, N. Marin, C. Schwan, S. Kuehne, N. P. Minton, W. A. Petri

Abstract

Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. We have previously shown that CDT interacts with the TLR2/6 heterodimer to induce inflammation, and in this study we further explore this interaction as well as the contribution of the separate components of CDT, CDTa and CDTb. We found that the binding component, CDTb, is capable of inducing inflammation. Additionally, complementation of a CDT-deficient C. difficile strain with CDTb alone restored virulence in a hamster model of C. difficile infection. Overall, this study demonstrates that the binding component of C. difficile binary toxin contributes to virulence during infection.

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