Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile
Qiwen Dong,
Huaiying Lin,
Marie-Maude Allen,
Julian R. Garneau,
Jonathan K. Sia,
Rita C. Smith,
Fidel Haro,
Tracy McMillen,
Rosemary L. Pope,
Carolyn Metcalfe,
Victoria Burgo,
Che Woodson,
Nicholas Dylla,
Claire Kohout,
Anitha Sundararajan,
Evan S. Snitkin,
Vincent B. Young,
Louis-Charles Fortier,
Mini Kamboj,
Eric G. Pamer
Affiliations
Qiwen Dong
Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Corresponding author
Huaiying Lin
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Marie-Maude Allen
Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada
Julian R. Garneau
Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada
Jonathan K. Sia
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Rita C. Smith
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Fidel Haro
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Tracy McMillen
Infection Control, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Rosemary L. Pope
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
Carolyn Metcalfe
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Victoria Burgo
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Che Woodson
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Nicholas Dylla
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Claire Kohout
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Anitha Sundararajan
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
Evan S. Snitkin
Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Vincent B. Young
Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI 48109, USA
Louis-Charles Fortier
Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada
Mini Kamboj
Infection Control, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Eric G. Pamer
Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
Summary: Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains. We test 23 epidemic ST1 C. difficile clinical isolates for their virulence in mice. All isolates encode a complete Tcd pathogenicity locus and achieve similar colonization densities. However, disease severity varies from lethal to avirulent infections. Genomic analysis of avirulent isolates reveals a 69-bp deletion in the cdtR gene, which encodes a response regulator for binary toxin expression. Deleting the 69-bp sequence in virulent R20291 strain renders it avirulent in mice with reduced toxin gene transcription. Our study demonstrates that a natural deletion within cdtR attenuates virulence in the epidemic ST1 C. difficile isolates without reducing colonization and persistence. Distinguishing strains on the basis of cdtR may enhance the specificity of diagnostic tests for C. difficile colitis.
