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

Cell Reports (Aug 2023)

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

Journal volume & issue: Vol. 42, no. 8
p. 112861

Abstract

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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.

CP: Microbiology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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