Clostridioides difficileBinary Toxin Binding Component Increases Virulence in a Hamster Model
Open Access
- 31 January 2023
- journal article
- research article
- Published by Oxford University Press (OUP) in Open Forum Infectious Diseases
- Vol. 10 (3), ofad040
- https://doi.org/10.1093/ofid/ofad040
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. While 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. 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. While 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. Overall, this study demonstrates that the binding component of C. difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection.Funding Information
- National Institutes of Health (R01 AI124214, T32AI007496, F32DK124048)
- Marie Curie Clospore ITN (642068)
- NIHR Nottingham Biomedical Research Centre (BRC-1215-20003)
This publication has 24 references indexed in Scilit:
- Markers of Intestinal Inflammation, Not Bacterial Burden, Correlate With Clinical Outcomes in Clostridium difficile InfectionClinical Infectious Diseases, 2013
- Expanding the Repertoire of Gene Tools for Precise Manipulation of the Clostridium difficile Genome: Allelic Exchange Using pyrE AllelesPLOS ONE, 2013
- Lipolysis-stimulated lipoprotein receptor (LSR) is the host receptor for the binary toxin Clostridium difficile transferase (CDT)Proceedings of the National Academy of Sciences of the United States of America, 2011
- Infection of hamsters with the UK Clostridium difficile ribotype 027 outbreak strain R20291Journal of Medical Microbiology, 2011
- The role of toxin A and toxin B in Clostridium difficile infectionNature, 2010
- A m ariner -Based Transposon System for In Vivo Random Mutagenesis of Clostridium difficileApplied and Environmental Microbiology, 2010
- Clostridium difficile Toxin CDT Induces Formation of Microtubule-Based Protrusions and Increases Adherence of BacteriaPLoS Pathogens, 2009
- Clostridium difficile infection: new developments in epidemiology and pathogenesisNature Reviews Microbiology, 2009
- Clostridium difficileToxins: Mechanism of Action and Role in DiseaseClinical Microbiology Reviews, 2005
- Conjugative plasmid transfer from Escherichia coli to Clostridium acetobutylicumJournal of General Microbiology, 1990