Susceptibility of hamsters to Clostridium difficile isolates of differing toxinotype

Anthony M. Buckley, Janice Spencer, Lindsay M. Maclellan, Denise Candlish, June J. Irvine, Gillian R. Douce*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ,21,000cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) & BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdBand CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial & toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression.
Original languageEnglish
Article numbere64121
Number of pages10
JournalPLOS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 21 May 2013

Keywords

  • Clostridium difficile
  • hamsters
  • toxins
  • bacterial spores
  • Clindamycin
  • Neutrophils
  • colon
  • body temperature

ASJC Scopus subject areas

  • General

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