tcdC genotypes associated with severe TcdC truncation in an epidemic clone and other strains of Clostridium difficile - PubMed (original) (raw)

tcdC genotypes associated with severe TcdC truncation in an epidemic clone and other strains of Clostridium difficile

Scott R Curry et al. J Clin Microbiol. 2007 Jan.

Erratum in

Abstract

Severe Clostridium difficile associated disease is associated with outbreaks of the recently described BI/NAP1 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 samples 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 amino acid residues), whereas 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 five 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 amino acid 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 probably 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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Figures

FIG. 1.

FIG. 1.

Comparison of TcdC nucleotide and amino acid sequences to the published sequence for the reference strain VPI10463. Dots and dashes indicate identical bases and deletions, respectively. Only amino acid changes are depicted. Stop codons are underlined. Genotype tcdC-sc2 is not depicted but is identical to tcdC-sc1 with the exception of an inserted nucleotide (t) in the untranslated region at position 212.

FIG. 1.

FIG. 1.

Comparison of TcdC nucleotide and amino acid sequences to the published sequence for the reference strain VPI10463. Dots and dashes indicate identical bases and deletions, respectively. Only amino acid changes are depicted. Stop codons are underlined. Genotype tcdC-sc2 is not depicted but is identical to tcdC-sc1 with the exception of an inserted nucleotide (t) in the untranslated region at position 212.

FIG. 2.

FIG. 2.

Minimum-spanning tree of MLVA data depicting genetic relatedness of 199 isolates of C. difficile from cases of CDAD at UPMC-P in 2001 and 2005. Each circle depicts one MLVA genotype, with the STRD between adjacent isolates displayed in gray. Where no numeral is shown, the STRD equals 1. STRDs of ≥11 are depicted with dashed lines. Clouds of gray surround isolates with an STRD of ≤2; these complexes represent closely related isolates. White circles depict genotypes represented by one isolate; light gray circles with black numerals, dark gray circles with white numerals, and black circles with white numerals depict genotypes represented by 2, 3, and ≥5 isolates, respectively. The circles are labeled with the tcdC genotype described in Fig. 1 (wild-type tcdC = 0, tcdC-A = A, _tcdC-_B = B, _tcdC-_sc1 = 1, tcdC-sc2 = 2, tcdC-sc3 = 3, etc.); available REA types are displayed below the tcdC genotype. The tree has been redrawn for ease of viewing and is not to scale.

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