Importance of Toxin A, Toxin B, and CDT in Virulence of an Epidemic Clostridium Difficile Strain

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2013 Aug 13

PMID 23935202

Citations 112

Authors

Sarah A Kuehne

Mark M Collery

Michelle L Kelly

Stephen T Cartman

Alan Cockayne

Nigel P Minton

Affiliations

Soon will be listed here.

Abstract

Clostridium difficile infection is the main cause of healthcare-acquired diarrhea in the developed world. In addition to the main virulence factors toxin A and B, epidemic, PCR Ribotype 027 strains, such as R20291, produce a third toxin, CDT. To develop effective medical countermeasures, it is important to understand the importance of each toxin. Accordingly, we created all possible combinations of isogenic toxin mutants of R20291 and assessed their virulence. We demonstrated that either toxin A or toxin B alone can cause fulminant disease in the hamster infection model and present tantalizing data that C. difficile toxin may also contribute to virulence.

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References

Popoff M, Rubin E, Gill D, Boquet P . Actin-specific ADP-ribosyltransferase produced by a Clostridium difficile strain. Infect Immun. 1988; 56(9):2299-306. PMC: 259564. DOI: 10.1128/iai.56.9.2299-2306.1988. View

Kuehne S, Minton N . ClosTron-mediated engineering of Clostridium. Bioengineered. 2012; 3(4):247-54. PMC: 3476875. DOI: 10.4161/bioe.21004. View

Cartman S, Heap J, Kuehne S, Cockayne A, Minton N . The emergence of 'hypervirulence' in Clostridium difficile. Int J Med Microbiol. 2010; 300(6):387-95. DOI: 10.1016/j.ijmm.2010.04.008. View

McEllistrem M, Carman R, Gerding D, Genheimer C, Zheng L . A hospital outbreak of Clostridium difficile disease associated with isolates carrying binary toxin genes. Clin Infect Dis. 2005; 40(2):265-72. DOI: 10.1086/427113. View

Geric B, Carman R, Rupnik M, Genheimer C, Sambol S, Lyerly D . Binary toxin-producing, large clostridial toxin-negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters. J Infect Dis. 2006; 193(8):1143-50. DOI: 10.1086/501368. View

Heap J, Kuehne S, Ehsaan M, Cartman S, Cooksley C, Scott J . The ClosTron: Mutagenesis in Clostridium refined and streamlined. J Microbiol Methods. 2009; 80(1):49-55. DOI: 10.1016/j.mimet.2009.10.018. View

Ballard J . Medical microbiology: A toxin contest. Nature. 2010; 467(7316):665-6. DOI: 10.1038/467665a. View

Lyras D, OConnor J, Howarth P, Sambol S, Carter G, Phumoonna T . Toxin B is essential for virulence of Clostridium difficile. Nature. 2009; 458(7242):1176-9. PMC: 2679968. DOI: 10.1038/nature07822. View

Kuehne S, Cartman S, Heap J, Kelly M, Cockayne A, Minton N . The role of toxin A and toxin B in Clostridium difficile infection. Nature. 2010; 467(7316):711-3. DOI: 10.1038/nature09397. View

10.

Williams D, Young D, Young M . Conjugative plasmid transfer from Escherichia coli to Clostridium acetobutylicum. J Gen Microbiol. 1990; 136(5):819-26. DOI: 10.1099/00221287-136-5-819. View

11.

Holmer C, Zurbuchen U, Siegmund B, Reichelt U, Buhr H, Ritz J . Clostridium difficile infection of the small bowel--two case reports with a literature survey. Int J Colorectal Dis. 2010; 26(2):245-51. DOI: 10.1007/s00384-010-1001-y. View

12.

Schwan C, Stecher B, Tzivelekidis T, van Ham M, Rohde M, Hardt W . Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria. PLoS Pathog. 2009; 5(10):e1000626. PMC: 2757728. DOI: 10.1371/journal.ppat.1000626. View

13.

Carman R, Stevens A, Lyerly M, Hiltonsmith M, Stiles B, Wilkins T . Clostridium difficile binary toxin (CDT) and diarrhea. Anaerobe. 2011; 17(4):161-5. DOI: 10.1016/j.anaerobe.2011.02.005. View

14.

Goldenberg S, French G . Lack of association of tcdC type and binary toxin status with disease severity and outcome in toxigenic Clostridium difficile. J Infect. 2011; 62(5):355-62. DOI: 10.1016/j.jinf.2011.03.001. View