1887

Abstract

is the main cause of antibiotic-associated disease, a disease of high socio-economical importance that has recently been compounded by the global spread of the 027 (BI/NAP1/027) ribotype. . cases attributed to ribotype 027 strains have high recurrence rates (up to 36 %) and increased disease severity. The hamster model of infection is widely accepted as an appropriate model for studying aspects of . host–pathogen interactions. Using this model we characterized the infection kinetics of the UK 2006 outbreak strain, R20291. Hamsters were orally given a dose of clindamycin, followed 5 days later with 10 000 . spores. All 100 % of the hamsters succumbed to infection with a mean time to the clinical end point of 46.7 h. Colonization of the caecum and colon were observed 12 h post-infection reaching a maximum of approximately 3×10 c.f.u. per organ, but spores were not detected until 24 h post-infection. At 36 h post-infection . numbers increased significantly to approximately 6×10 c.f.u. per organ where numbers remained high until the clinical end point. Increasing levels of toxin production coincided with increases in . numbers in organs reaching a maximum at 36 h post-infection in the caecum. Epithelial destruction and polymorphonuclear leukocyte (PMN) recruitment occurred early on during infection (24 h) accumulating as gross microvilli damage, luminal PMN influx, and blood associated with mucosal muscle and microvilli. These data describe the fatal infection kinetics of the clinical UK epidemic . strain R20291 in the hamster infection model.

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2011-08-01
2019-09-15
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References

  1. Bartlett J. G. , Onderdonk A. B. , Cisneros R. L. , Kasper D. L. . ( 1977; ). Clindamycin-associated colitis due to a toxin-producing species of Clostridium in hamsters. . J Infect Dis 136:, 701–705. [CrossRef].[PubMed].
    [Google Scholar]
  2. Carter G. P. , Purdy D. , Williams P. , Minton N. P. . ( 2005; ). Quorum sensing in Clostridium difficile: analysis of a LuxS-type signalling system. . J Med Microbiol 54:, 119–127. [CrossRef].[PubMed].
    [Google Scholar]
  3. Cartman S. T. , Heap J. T. , Kuehne S. A. , Cockayne A. , Minton N. P. . ( 2010; ). The emergence of ‘hypervirulence’ in Clostridium difficile . . Int J Med Microbiol 300:, 387–395. [CrossRef].[PubMed].
    [Google Scholar]
  4. Geric B. , Carman R. J. , Rupnik M. , Genheimer C. W. , Sambol S. P. , Lyerly D. M. , Gerding D. N. , Johnson S. . ( 2006; ). Binary toxin-producing, large clostridial toxin-negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters. . J Infect Dis 193:, 1143–1150. [CrossRef].[PubMed].
    [Google Scholar]
  5. Goulding D. , Thompson H. , Emerson J. , Fairweather N. F. , Dougan G. , Douce G. R. . ( 2009; ). Distinctive profiles of infection and pathology in hamsters infected with Clostridium difficile strains 630 and B1. . Infect Immun 77:, 5478–5485. [CrossRef].[PubMed].
    [Google Scholar]
  6. HC ( 2006; ). Investigation into Outbreaks of Clostridium difficile at Stoke Mandeville Hospital, Buckinghamshire Hospitals NHS Trust, http://www.cqc.org.uk/_db/_documents/Stoke_Mandeville.pdf, ISBN: 1-84562-103-4. London:: Healthcare Commission;.
    [Google Scholar]
  7. Larson H. E. , Borriello S. P. . ( 1990; ). Quantitative study of antibiotic-induced susceptibility to Clostridium difficile enterocecitis in hamsters. . Antimicrob Agents Chemother 34:, 1348–1353.[PubMed].[CrossRef]
    [Google Scholar]
  8. Lawley T. D. , Croucher N. J. , Yu L. , Clare S. , Sebaihia M. , Goulding D. , Pickard D. J. , Parkhill J. , Choudhary J. , Dougan G. . ( 2009; ). Proteomic and genomic characterization of highly infectious Clostridium difficile 630 spores. . J Bacteriol 191:, 5377–5386. [CrossRef].[PubMed].
    [Google Scholar]
  9. Marsh J. W. , O’Leary M. M. , Shutt K. A. , Pasculle A. W. , Johnson S. , Gerding D. N. , Muto C. A. , Harrison L. H. . ( 2006; ). Multilocus variable-number tandem-repeat analysis for investigation of Clostridium difficile transmission in hospitals. . J Clin Microbiol 44:, 2558–2566. [CrossRef].[PubMed].
    [Google Scholar]
  10. Razaq N. , Sambol S. , Nagaro K. , Zukowski W. , Cheknis A. , Johnson S. , Gerding D. N. . ( 2007; ). Infection of hamsters with historical and epidemic BI types of Clostridium difficile . . J Infect Dis 196:, 1813–1819. [CrossRef].[PubMed].
    [Google Scholar]
  11. Rolfe R. D. , Song W. . ( 1993; ). Purification of a functional receptor for Clostridium difficile toxin A from intestinal brush border membranes of infant hamsters. . Clin Infect Dis 16: Suppl. 4 S219–S227. [CrossRef].[PubMed].
    [Google Scholar]
  12. Rupnik M. , Avesani V. , Janc M. , Von Eichel-Streiber C. , Delmée M. . ( 1998; ). A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. . J Clin Microbiol 36:, 2240–2247.[PubMed].
    [Google Scholar]
  13. Sambol S. P. , Tang J. K. , Merrigan M. M. , Johnson S. , Gerding D. N. . ( 2001; ). Infection of hamsters with epidemiologically important strains of Clostridium difficile . . J Infect Dis 183:, 1760–1766. [CrossRef].[PubMed].
    [Google Scholar]
  14. Schwan C. , Stecher B. , Tzivelekidis T. , Van Ham M. , Rohde M. , Hardt W. D. , Wehland J. , Aktories K. . ( 2009; ). Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria. . PLoS Pathog 5:, e1000626. [CrossRef].[PubMed].
    [Google Scholar]
  15. Stabler R. A. , He M. , Dawson L. , Martin M. , Valiente E. , Corton C. , Lawley T. D. , Sebaihia M. , Quail M. A. et al. ( 2009; ). Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium. . Genome Biol 10:, R102. [CrossRef].[PubMed].
    [Google Scholar]
  16. Stubbe H. , Berdoz J. , Kraehenbuhl J. P. , Corthésy B. . ( 2000; ). Polymeric IgA is superior to monomeric IgA and IgG carrying the same variable domain in preventing Clostridium difficile toxin A damaging of T84 monolayers. . J Immunol 164:, 1952–1960.[PubMed].[CrossRef]
    [Google Scholar]
  17. Underwood S. , Guan S. , Vijayasubhash V. , Baines S. D. , Graham L. , Lewis R. J. , Wilcox M. H. , Stephenson K. . ( 2009; ). Characterization of the sporulation initiation pathway of Clostridium difficile and its role in toxin production. . J Bacteriol 191:, 7296–7305. [CrossRef].[PubMed].
    [Google Scholar]
  18. Warny M. , Pepin J. , Fang A. , Killgore G. , Thompson A. , Brazier J. , Frost E. , McDonald L. C. . ( 2005; ). Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. . Lancet 366:, 1079–1084. [CrossRef].[PubMed].
    [Google Scholar]
  19. Wilcox M. H. , Cunniffe J. G. , Trundle C. , Redpath C. . ( 1996; ). Financial burden of hospital-acquired Clostridium difficile infection. . J Hosp Infect 34:, 23–30. [CrossRef].[PubMed].
    [Google Scholar]
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