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J. Clin. Microbiol. doi:10.1128/JCM.01599-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

TcdC Genotypes Predicting Severe TcdC Truncation in an Epidemic Clone and Other Strains of Clostridium difficile

Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Division of Hospital Epidemiology and Infection Control and Division of Infectious Diseases, University of Pittsburgh Medical Center, Presbyterian Campus, Division of Microbiology, Department of Pathology, University of Pittsburgh School of Medicine, Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health

^* To whom correspondence should be addressed. Email: lharriso{at}edc.pitt.edu.

	Abstract

Severe Clostridium difficile associated disease is associated with outbreaks of the recently described BI/NAPI epidemic clone. This clone is characterized by an 18 bp deletion in the tcdC gene and increased production of toxins A and B in vitro. TcdC is a putative negative regulator of toxin A&B production. We characterized tcdC genotypes from a collection of C. difficile isolates from a hospital that experienced an outbreak caused by the BI/NAP1 epidemic clone. Sequence analysis of tcdC was performed on DNA isolated from 199 toxigenic C. difficile isolates (31% BI/NAP1) from 2001 and 2005. Sequences obtained from 36 (18.6%) isolates predicted wild type TcdC (232 a.a. residues) while 12 (6.1%) isolates had tcdC genotypes with previously described 18 or 39 bp deletions. The remaining isolates comprised 15 unique genotypes. Of these, 5 genotypes contain 18 or 36 bp deletions. Of these 5 genotypes, one is characterized by a single nucleotide deletion at position 117 resulting in a frameshift that introduces a stop codon at position 196, truncating the predicted TcdC to 65 a.a. residues. All 62 of the isolates in this collection comprising the epidemic clone are characterized by this genotype. This result suggests that severe truncation of TcdC is responsible for the increased toxin production observed in strains belonging to the BI/NAP1 clone and that the 18 bp deletion is likely irrelevant to TcdC function. Further investigations are required to determine the effect of this and other tcdC genotypes on toxin production and clinical disease.

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