Kasendra, Magdalena Julia
(2014)
Clostridium difficile toxins facilitate bacterial colonization by modulating the fence and gate function of colonic epithelium
, [Dissertation thesis], Alma Mater Studiorum Università di Bologna.
Dottorato di ricerca in
Biologia cellulare e molecolare, 26 Ciclo. DOI 10.6092/unibo/amsdottorato/6364.
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Abstract
The contribution of Clostridium difficile toxin A and B (TcdA and TcdB) to cellular intoxication has been extensively studied, but their impact on bacterial colonization remains unclear. By setting-up two- and three-dimensional in vitro models of polarized gut epithelium, we investigated how C. difficile infection is affected by host cell polarity and whether TcdA and TcdB contribute to such events. Indeed, we observed that C. difficile adhesion and penetration of the epithelial barrier is substantially enhanced in poorly polarized or EGTA-treated cells, indicating that bacteria bind preferentially to the basolateral cell surface. In this context, we demonstrated that sub-lethal concentrations of C. difficile TcdA are able to alter cell polarity by causing redistribution of plasma membrane components between distinct surface domains. Taken together, the data suggest that toxin-mediated modulation of host cell organization may account for the capacity of this opportunistic pathogen to gain access to basolateral receptors leading to a successful colonization of the colonic mucosa.
Abstract
The contribution of Clostridium difficile toxin A and B (TcdA and TcdB) to cellular intoxication has been extensively studied, but their impact on bacterial colonization remains unclear. By setting-up two- and three-dimensional in vitro models of polarized gut epithelium, we investigated how C. difficile infection is affected by host cell polarity and whether TcdA and TcdB contribute to such events. Indeed, we observed that C. difficile adhesion and penetration of the epithelial barrier is substantially enhanced in poorly polarized or EGTA-treated cells, indicating that bacteria bind preferentially to the basolateral cell surface. In this context, we demonstrated that sub-lethal concentrations of C. difficile TcdA are able to alter cell polarity by causing redistribution of plasma membrane components between distinct surface domains. Taken together, the data suggest that toxin-mediated modulation of host cell organization may account for the capacity of this opportunistic pathogen to gain access to basolateral receptors leading to a successful colonization of the colonic mucosa.
Tipologia del documento
Tesi di dottorato
Autore
Kasendra, Magdalena Julia
Supervisore
Co-supervisore
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Ciclo
26
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
C. difficile, toxins, cell polarity, adhesion
URN:NBN
DOI
10.6092/unibo/amsdottorato/6364
Data di discussione
11 Aprile 2014
URI
Altri metadati
Tipologia del documento
Tesi di dottorato
Autore
Kasendra, Magdalena Julia
Supervisore
Co-supervisore
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Ciclo
26
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
C. difficile, toxins, cell polarity, adhesion
URN:NBN
DOI
10.6092/unibo/amsdottorato/6364
Data di discussione
11 Aprile 2014
URI
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