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Role of Clostridium difficile Toxins in Antibiotic-Associated Diarrhea and Pseudomembranous Colitis

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Microbial Toxins

Part of the book series: Toxinology ((TOXI))

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Abstract

Clostridium difficile is a nosocomial agent affecting immunocompromised populations under antibiotic treatment. The clinical manifestations induced by this bacterium range from mild antibiotic-associated diarrhea to potentially fatal pseudomembranous colitis. Traditionally, all the signs and symptoms produced by C. difficile have been associated to the production of two toxins, toxin A and toxin B. Both toxins belong to the family of large clostridial cytotoxins (LCTs), and their mechanism of action relies on a series of complex steps. First, these toxins recognize cell-surface located receptors allowing the entrance in membrane-surrounded compartments. The toxins are then translocated through acid sensing-dependent conformational changes and the enzymatically active domain is released into the cytosol through an autoprocessing activity. This enzymatic domain modifies through glucosylation of small guanosine triphosphatase (GTPases) from the Rho and Ras families. Consequently, the signal transduction pathways mediated by these proteins are interrupted leading to the corresponding cytoskeletal alterations and different effects which might finally result in different types of cell death. In vivo, these toxins induce toxicity on epithelial cells lining the intestinal mucosa and induce a severe inflammatory reaction characterized by the recruitment of neutrophils and secretion of several cytokines. It is precisely a combination of dead intestinal epithelial cells combined with polymorphonuclear immune cells that constitutes the characteristic pseudomembrane observed in diarrheic depositions by patients suffering complications of this infection. In this chapter, the clinical manifestations induced by C. difficile toxins, the cellular consequences of their mechanism of action and the evolution of the pathogenicity locus where they are encoded are discussed in detail.

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Authors and Affiliations

  1. Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San Pedro, San José, Costa Rica

    Diana López-Ureña, Carlos Quesada-Gómez, César Rodríguez & Esteban Chaves-Olarte

Authors
  1. Diana López-Ureña
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  2. Carlos Quesada-Gómez
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  3. César Rodríguez
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  4. Esteban Chaves-Olarte
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Corresponding authors

Correspondence to Diana López-Ureña , Carlos Quesada-Gómez , César Rodríguez or Esteban Chaves-Olarte .

Editor information

Editors and Affiliations

  1. Biology Department, Wilson College, Chambersburg, Pennsylvania, USA

    Brad Stiles

  2. Department of Biochemistry, School of Medicine and Instituto Clodomiro Picado, Faculty of Microbiology, University of Costa Rica, San Pedro de Montes de Oca, Costa Rica

    Alberto Alape-Girón

  3. Department of Pathology and Microbiology, Université de Montréal, Saint-Hyacinthe, Québec, Canada

    J. Daniel Dubreuil

  4. College of Pharmacy, Roseman University of Health Sciences, Henderson, Nevada, USA

    Manas Mandal

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López-Ureña, D., Quesada-Gómez, C., Rodríguez, C., Chaves-Olarte, E. (2018). Role of Clostridium difficile Toxins in Antibiotic-Associated Diarrhea and Pseudomembranous Colitis. In: Stiles, B., Alape-Girón, A., Dubreuil, J., Mandal, M. (eds) Microbial Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6449-1_17

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