Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile .

Autor: Dong Q; Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Lin H; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Allen MM; Department of Microbiology and Infectious Diseases, Universite de Sherbrooke, Sherbrooke, Quebec, Canada., Garneau JR; Department of Microbiology and Infectious Diseases, Universite de Sherbrooke, Sherbrooke, Quebec, Canada., Sia JK; Immunology Program, Memorial Sloan Kettering Cancer Center, New York City, New York, USA., Smith RC; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Haro F; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., McMillen T; Infection Control, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Pope RL; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA.; Committee on Immunology, University of Chicago, Chicago, Illinois, USA., Metcalfe C; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Burgo V; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Woodson C; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Dylla N; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Kohout C; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Sundararajan A; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Snitkin ES; Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Young VB; Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.; Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI, USA., Fortier LC; Department of Microbiology and Infectious Diseases, Universite de Sherbrooke, Sherbrooke, Quebec, Canada., Kamboj M; Infection Control, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Pamer EG; Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA.; Committee on Immunology, University of Chicago, Chicago, Illinois, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Jan 12. Date of Electronic Publication: 2023 Jan 12.
DOI: 10.1101/2023.01.12.523823
Abstrakt: Clostridioides difficile (C. difficile) , a leading cause of nosocomial infection, produces toxins that damage the colonic epithelium and results in colitis that varies from mild to fulminant. Variation in disease severity is poorly understood and has been attributed to host factors (age, immune competence and intestinal microbiome composition) and/or virulence differences between C. difficile strains, with some, such as the epidemic BI/NAP1/027 (MLST1) strain, being associated with greater virulence. We tested 23 MLST1(ST1) C. difficile clinical isolates for virulence in antibiotic-treated C57BL/6 mice. All isolates encoded a complete Tcd pathogenicity locus and achieved similar colonization densities in mice. Disease severity varied, however, with 5 isolates causing lethal infections, 16 isolates causing a range of moderate infections and 2 isolates resulting in no detectable disease. The avirulent ST1 isolates did not cause disease in highly susceptible Myd88 -/- or germ-free mice. Genomic analysis of the avirulent isolates revealed a 69 base-pair deletion in the N-terminus of the cdtR gene, which encodes a response regulator for binary toxin (CDT) expression. Genetic deletion of the 69 base-pair cdtR sequence in the highly virulent ST1 R20291 C. difficile strain rendered it avirulent and reduced toxin gene transcription in cecal contents. Our study demonstrates that a natural deletion within cdtR attenuates virulence in the epidemic ST1 C. difficile strain without reducing colonization and persistence in the gut. Distinguishing strains on the basis of cdtR may enhance the specificity of diagnostic tests for C. difficile colitis.
Databáze: MEDLINE