Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain

Sze K Lim, Rhonda Lee Stuart, Kate Elizabeth Mackin, Glen Paul Carter, Despina Kotsanas, Michelle J Francis, Marion Easton, Karolina Dimovski, Briony Elliott, Thomas Victor Riley, Geoffrey G Hogg, Eldho Paul, Tony Korman, Torsten Seemann, Timothy Paul Stinear, Dena Lyras, Grant Adam Jenkin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND: We identified 12 patients with Clostridium difficile infection between July 2011 and March 2012 from whom an unusual C. difficile strain was isolated. This strain had a single-nucleotide deletion of the tcdC gene at position 117 and binary toxin genes, which are characteristic of the hypervirulent ribotype (RT) 027 strain. METHODS: A retrospective cohort study of 12 patients infected with C. difficile RT244 and 24 patients infected with non-RT244/non-RT027 strains matched for place of diagnosis and time of collection of specimen was performed. We performed whole-genome sequencing to understand the relationship of the RT244 strain to other C. difficile strains and further understand its virulence potential. RESULTS: Clostridium difficile RT244 was associated with more severe disease and a higher mortality rate. Phylogenomic analysis using core genome single-nucleotide polymorphisms showed that RT244 is in the same genetic clade (clade 2) as RT027 but is distinct from all RT027 strains. The pathogenicity locus of the RT244 strain encodes a variant toxin B, and this was confirmed by demonstration of Clostridium sordellii-like cytopathic effect on Vero cells. Toxin B production in culture supernatants was lower than that seen with a RT027 strain. CONCLUSIONS: Our findings demonstrate the pathogenic potential of this RT244 C. difficile strain and emphasize the importance of ongoing surveillance for emergent strains.
Original languageEnglish
Pages (from-to)1723 - 1730
Number of pages8
JournalClinical Infectious Diseases
Volume58
Issue number12
DOIs
Publication statusPublished - 2014

Cite this

Lim, Sze K ; Stuart, Rhonda Lee ; Mackin, Kate Elizabeth ; Carter, Glen Paul ; Kotsanas, Despina ; Francis, Michelle J ; Easton, Marion ; Dimovski, Karolina ; Elliott, Briony ; Riley, Thomas Victor ; Hogg, Geoffrey G ; Paul, Eldho ; Korman, Tony ; Seemann, Torsten ; Stinear, Timothy Paul ; Lyras, Dena ; Jenkin, Grant Adam. / Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain. In: Clinical Infectious Diseases. 2014 ; Vol. 58, No. 12. pp. 1723 - 1730.
@article{f8ecaa560f9745bfaabd8aa37f42c3d5,
title = "Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain",
abstract = "BACKGROUND: We identified 12 patients with Clostridium difficile infection between July 2011 and March 2012 from whom an unusual C. difficile strain was isolated. This strain had a single-nucleotide deletion of the tcdC gene at position 117 and binary toxin genes, which are characteristic of the hypervirulent ribotype (RT) 027 strain. METHODS: A retrospective cohort study of 12 patients infected with C. difficile RT244 and 24 patients infected with non-RT244/non-RT027 strains matched for place of diagnosis and time of collection of specimen was performed. We performed whole-genome sequencing to understand the relationship of the RT244 strain to other C. difficile strains and further understand its virulence potential. RESULTS: Clostridium difficile RT244 was associated with more severe disease and a higher mortality rate. Phylogenomic analysis using core genome single-nucleotide polymorphisms showed that RT244 is in the same genetic clade (clade 2) as RT027 but is distinct from all RT027 strains. The pathogenicity locus of the RT244 strain encodes a variant toxin B, and this was confirmed by demonstration of Clostridium sordellii-like cytopathic effect on Vero cells. Toxin B production in culture supernatants was lower than that seen with a RT027 strain. CONCLUSIONS: Our findings demonstrate the pathogenic potential of this RT244 C. difficile strain and emphasize the importance of ongoing surveillance for emergent strains.",
author = "Lim, {Sze K} and Stuart, {Rhonda Lee} and Mackin, {Kate Elizabeth} and Carter, {Glen Paul} and Despina Kotsanas and Francis, {Michelle J} and Marion Easton and Karolina Dimovski and Briony Elliott and Riley, {Thomas Victor} and Hogg, {Geoffrey G} and Eldho Paul and Tony Korman and Torsten Seemann and Stinear, {Timothy Paul} and Dena Lyras and Jenkin, {Grant Adam}",
year = "2014",
doi = "10.1093/cid/ciu203",
language = "English",
volume = "58",
pages = "1723 -- 1730",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "12",

}

Lim, SK, Stuart, RL, Mackin, KE, Carter, GP, Kotsanas, D, Francis, MJ, Easton, M, Dimovski, K, Elliott, B, Riley, TV, Hogg, GG, Paul, E, Korman, T, Seemann, T, Stinear, TP, Lyras, D & Jenkin, GA 2014, 'Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain' Clinical Infectious Diseases, vol. 58, no. 12, pp. 1723 - 1730. https://doi.org/10.1093/cid/ciu203

Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain. / Lim, Sze K; Stuart, Rhonda Lee; Mackin, Kate Elizabeth; Carter, Glen Paul; Kotsanas, Despina; Francis, Michelle J; Easton, Marion; Dimovski, Karolina; Elliott, Briony; Riley, Thomas Victor; Hogg, Geoffrey G; Paul, Eldho; Korman, Tony; Seemann, Torsten; Stinear, Timothy Paul; Lyras, Dena; Jenkin, Grant Adam.

In: Clinical Infectious Diseases, Vol. 58, No. 12, 2014, p. 1723 - 1730.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain

AU - Lim, Sze K

AU - Stuart, Rhonda Lee

AU - Mackin, Kate Elizabeth

AU - Carter, Glen Paul

AU - Kotsanas, Despina

AU - Francis, Michelle J

AU - Easton, Marion

AU - Dimovski, Karolina

AU - Elliott, Briony

AU - Riley, Thomas Victor

AU - Hogg, Geoffrey G

AU - Paul, Eldho

AU - Korman, Tony

AU - Seemann, Torsten

AU - Stinear, Timothy Paul

AU - Lyras, Dena

AU - Jenkin, Grant Adam

PY - 2014

Y1 - 2014

N2 - BACKGROUND: We identified 12 patients with Clostridium difficile infection between July 2011 and March 2012 from whom an unusual C. difficile strain was isolated. This strain had a single-nucleotide deletion of the tcdC gene at position 117 and binary toxin genes, which are characteristic of the hypervirulent ribotype (RT) 027 strain. METHODS: A retrospective cohort study of 12 patients infected with C. difficile RT244 and 24 patients infected with non-RT244/non-RT027 strains matched for place of diagnosis and time of collection of specimen was performed. We performed whole-genome sequencing to understand the relationship of the RT244 strain to other C. difficile strains and further understand its virulence potential. RESULTS: Clostridium difficile RT244 was associated with more severe disease and a higher mortality rate. Phylogenomic analysis using core genome single-nucleotide polymorphisms showed that RT244 is in the same genetic clade (clade 2) as RT027 but is distinct from all RT027 strains. The pathogenicity locus of the RT244 strain encodes a variant toxin B, and this was confirmed by demonstration of Clostridium sordellii-like cytopathic effect on Vero cells. Toxin B production in culture supernatants was lower than that seen with a RT027 strain. CONCLUSIONS: Our findings demonstrate the pathogenic potential of this RT244 C. difficile strain and emphasize the importance of ongoing surveillance for emergent strains.

AB - BACKGROUND: We identified 12 patients with Clostridium difficile infection between July 2011 and March 2012 from whom an unusual C. difficile strain was isolated. This strain had a single-nucleotide deletion of the tcdC gene at position 117 and binary toxin genes, which are characteristic of the hypervirulent ribotype (RT) 027 strain. METHODS: A retrospective cohort study of 12 patients infected with C. difficile RT244 and 24 patients infected with non-RT244/non-RT027 strains matched for place of diagnosis and time of collection of specimen was performed. We performed whole-genome sequencing to understand the relationship of the RT244 strain to other C. difficile strains and further understand its virulence potential. RESULTS: Clostridium difficile RT244 was associated with more severe disease and a higher mortality rate. Phylogenomic analysis using core genome single-nucleotide polymorphisms showed that RT244 is in the same genetic clade (clade 2) as RT027 but is distinct from all RT027 strains. The pathogenicity locus of the RT244 strain encodes a variant toxin B, and this was confirmed by demonstration of Clostridium sordellii-like cytopathic effect on Vero cells. Toxin B production in culture supernatants was lower than that seen with a RT027 strain. CONCLUSIONS: Our findings demonstrate the pathogenic potential of this RT244 C. difficile strain and emphasize the importance of ongoing surveillance for emergent strains.

UR - http://cid.oxfordjournals.org/content/58/12/1723.full.pdf

U2 - 10.1093/cid/ciu203

DO - 10.1093/cid/ciu203

M3 - Article

VL - 58

SP - 1723

EP - 1730

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 12

ER -