Surface-layer (S-layer) of Human and Animal Clostridium Difficile Strains and Their Behaviour in Adherence to Epithelial Cells and Intestinal Colonization

Clostridium difficile is a frequent cause of severe, recurrent post-antibiotic diarrhoea and pseudomembranous colitis. The surface layer (S-layer) is the predominant outer surface component of C. difficile which is involved in pathogen-host interactions critical to pathogenesis. In this study, we characterized the S-layer protein A (SIpA) of animal and human strains belonging to different PCR-ribotypes (PR) and compared the in vitro adherence and in vivo colonization properties of strains showing different SIpA variants. Since each SIpA variant has been recently associated with an S-layer cassette, we were able to deduce the cassette for each of our strains. In this study, an identity of 99-100% was found among the SIpA of isolates belonging to PR 012, 014/020, 045 and 078. One exception was the SIpA of a poultry isolate, PR 014/020, which showed 99% identity with that of strain 0160, another PR 014/020 which contains an S-layer cassette 6. Interestingly, this cassette has also been found in a PR 018 strain, an emerging virulent type currently predominant in Italy. Five other SIpA variants (v014/020a-e) were identified in strains PR 014/020. In vitro adherence assays and in vivo colonization experiments were performed on five PR 014/020 strains: human 1064 (v014/020e), human 4684/08 (v014/020b), human Ill 106 (v078a), poultry P30 (v014/020d) and poultry PB90 (v014/020b) strains. Adhesion assays indicate that C. difficile strains vary in their capacity to adhere to cells in culture and that adhesion seems to be independent of the SIpA variant. Colonization properties were assessed in vivo using a dixenic mouse model of colonization. The kinetics of faecal shedding and caecal colonization were similar when human 4684/08 (v014/020b) strain was compared with human 1064 (v014/020e) and poultry PB90 (v014/02013) strain. In contrast, poultry P30 (v014/020d) strain outcompeted both human 4684/08 (v014/020b) and IT1106 (v078a) strains and its adherence to caeca at day 7 was significantly higher. The peculiar characteristics of C. difficile P30 seem to advantage it in colonizing the intestinal mice niche, increasing its ability to compete and adapt. The results obtained underline the need of an increased attention to the genetic evolution of C. difficile to prevent and limit the consequences of the emergence of increasingly virulent strains

Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins

AbstractClostridium difficile is the most important enteropathogen involved in gut nosocomial post-antibiotic infections. The emergence of hypervirulent strains has contributed to increased mortality and morbidity of CDI. The C. difficile toxins contribute directly to CDI-associated lesions of the gut, but other bacterial factors are needed for the bacteria to adhere and colonize the intestinal epithelium. The C. difficile flagella, which confer motility and chemotaxis for successful intestinal colonization, could play an additional role in bacterial pathogenesis by contributing to the inflammatory response of the host and mucosal injury. Indeed, by activating the TLR5, flagella can elicit activation of the MAPK and NF-κB cascades of cell signaling, leading to the secretion of pro-inflammatory cytokines. In the current study, we demonstrate, by using an animal model of CDI, a synergic effect of flagella and toxins in eliciting an inflammatory mucosal response. In this model, the absence of flagella dramatically decreases the degree of mucosal inflammation in mice and the sole presence of toxins without flagella was not enough to elicit epithelial lesions. These results highlight the important role of C. difficile flagella in eliciting mucosal lesions as long as the toxins exert their action on the epithelium.</jats:p

Prise en charge de la maladie de Parkinson

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

L'impact du sport sur le corps féminin

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Asthme et sport chez l'enfant ((cas de la natation))

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Les Agents stimulant l'erythropoiese (intérêt thérapeutique et détournements de leur usage dans le sport)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

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CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Información Investigador: Kansau Silva, Imad Nasib

DoctoradoMayo de 2003+58 274 2403154Facultad de [email protected]

Données actuelles sur clostridium difficile

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Utilisation hospitalière des antibiotiques (enjeux, politique et bon usage en France, analyse des consommations sur 4 ans à l'hôpital Antoine Béclère de Clamart)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF