Literature DB >> 24394234

The roles of toxin A and toxin B in Clostridium difficile infection: insights from the gnotobiotic piglet model.

Jennifer Steele1, Nicola Parry2, Saul Tzipori1.   

Abstract

We recently published our findings indicating that anti-TcdB antibodies were effective as treatment for C. difficile infection, but that anti-TcdA actually worsened prognosis in the gnotobiotic piglet model. To further investigate the roles of the two toxins, we administered purified toxins separately or together, systemically, to piglets and found that both toxins, either alone or together, are able to elicit severe lesions systemically and are also able to cross into the gut lumen and cause large intestinal lesions typical of infection. We also found that anti-TcdA administered before systemic challenge with TcdA again did not protect from development of disease, but, in this case, did not appear to worsen prognosis. Further work is still needed, but these findings add to the growing knowledge regarding the roles of the C. difficile toxins.

Entities:  

Keywords:  Clostridium difficile; TcdA; TcdB; anti-toxin antibodies; monoclonal antibodies; systemic toxins; toxemia; toxins

Mesh:

Substances:

Year:  2013        PMID: 24394234      PMCID: PMC4049938          DOI: 10.4161/gmic.26855

Source DB:  PubMed          Journal:  Gut Microbes        ISSN: 1949-0976


  14 in total

1.  Identification of Clostridium difficile toxin B cardiotoxicity using a zebrafish embryo model of intoxication.

Authors:  Elaine E Hamm; Daniel E Voth; Jimmy D Ballard
Journal:  Proc Natl Acad Sci U S A       Date:  2006-09-11       Impact factor: 11.205

2.  Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile-induced mortality in hamsters.

Authors:  Gregory J Babcock; Teresa J Broering; Hector J Hernandez; Robert B Mandell; Katherine Donahue; Naomi Boatright; Anne M Stack; Israel Lowy; Robert Graziano; Deborah Molrine; Donna M Ambrosino; William D Thomas
Journal:  Infect Immun       Date:  2006-09-11       Impact factor: 3.441

3.  The role of toxin A and toxin B in Clostridium difficile infection.

Authors:  Sarah A Kuehne; Stephen T Cartman; John T Heap; Michelle L Kelly; Alan Cockayne; Nigel P Minton
Journal:  Nature       Date:  2010-09-15       Impact factor: 49.962

4.  Treatment with monoclonal antibodies against Clostridium difficile toxins.

Authors:  Israel Lowy; Deborah C Molrine; Brett A Leav; Barbra M Blair; Roger Baxter; Dale N Gerding; Geoffrey Nichol; William D Thomas; Mark Leney; Susan Sloan; Catherine A Hay; Donna M Ambrosino
Journal:  N Engl J Med       Date:  2010-01-21       Impact factor: 91.245

5.  Differential effects of Clostridium difficile toxins A and B on rabbit ileum.

Authors:  G Triadafilopoulos; C Pothoulakis; M J O'Brien; J T LaMont
Journal:  Gastroenterology       Date:  1987-08       Impact factor: 22.682

6.  An ultrasensitive rapid immunocytotoxicity assay for detecting Clostridium difficile toxins.

Authors:  Xiangyun He; Jufang Wang; Jennifer Steele; Xingmin Sun; Weijia Nie; Saul Tzipori; Hanping Feng
Journal:  J Microbiol Methods       Date:  2009-04-23       Impact factor: 2.363

7.  Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.

Authors:  Claribel P Taylor; Sanjeev Tummala; Deborah Molrine; Lisa Davidson; Richard J Farrell; Anthony Lembo; Patricia L Hibberd; Israel Lowy; Ciaran P Kelly
Journal:  Vaccine       Date:  2008-05-07       Impact factor: 3.641

8.  Piglet models of acute or chronic Clostridium difficile illness.

Authors:  Jennifer Steele; Hanping Feng; Nicola Parry; Saul Tzipori
Journal:  J Infect Dis       Date:  2010-02-01       Impact factor: 5.226

9.  Expression of recombinant Clostridium difficile toxin A and B in Bacillus megaterium.

Authors:  Guilin Yang; Boping Zhou; Jufang Wang; Xiangyun He; Xingmin Sun; Weijia Nie; Saul Tzipori; Hanping Feng
Journal:  BMC Microbiol       Date:  2008-11-06       Impact factor: 3.605

10.  Toxin B is essential for virulence of Clostridium difficile.

Authors:  Dena Lyras; Jennifer R O'Connor; Pauline M Howarth; Susan P Sambol; Glen P Carter; Tongted Phumoonna; Rachael Poon; Vicki Adams; Gayatri Vedantam; Stuart Johnson; Dale N Gerding; Julian I Rood
Journal:  Nature       Date:  2009-03-01       Impact factor: 49.962

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  2 in total

1.  Influence of Binary Toxin Gene Detection and Decreased Susceptibility to Antibiotics among Clostridioides difficile Strains on Disease Severity: a Single-Center Study.

Authors:  Deiziane V S Costa; Natalie V S Pham; Rachel A Hays; David T Bolick; Sophia M Goldbeck; Melinda D Poulter; Sook C Hoang; Jae H Shin; Martin Wu; Cirle A Warren
Journal:  Antimicrob Agents Chemother       Date:  2022-07-21       Impact factor: 5.938

Review 2.  The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.

Authors:  Huimin Yu; Nesrin M Hasan; Julie G In; Mary K Estes; Olga Kovbasnjuk; Nicholas C Zachos; Mark Donowitz
Journal:  Annu Rev Physiol       Date:  2017-02-10       Impact factor: 22.163

  2 in total

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