New trends in Clostridium difficile virulence and pathogenesis

Denève, Cécile; Janoir, Claire; Poîlane, I.; Fantinato, C.; Collignon, Anne

doi:10.1016/s0924-8579(09)70012-3

Cited by 177 publications

(161 citation statements)

References 60 publications

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“…Once established in the GI tract, C. difficile expresses two large exotoxins, toxin A (TcdA) and toxin B (TcdB) (Jank & Aktories, 2008;Voth & Ballard, 2005). Delivery of TcdA and TcdB to the cytoplasmic compartment of epithelial cells then leads to glucosylation of Rho family GTPases, resulting in disorganization of the host cell cytoskeleton (Deneve et al, 2009). This results in the loosening of tight junctions between adjacent intestinal epithelial cells ultimately leading to inflammation and diarrhoea.…”

Section: Introductionmentioning

confidence: 99%

“…To cause clinical illness, C. difficile first penetrates the mucus layer covering the epithelial surface of the gastrointestinal (GI) tract; a strategy that is most likely facilitated by flagella and proteases (Deneve et al, 2009;Tasteyre et al, 2001). Once established in the GI tract, C. difficile expresses two large exotoxins, toxin A (TcdA) and toxin B (TcdB) (Jank & Aktories, 2008;Voth & Ballard, 2005).…”

Section: Introductionmentioning

confidence: 99%

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A real-time quantitative PCR assay for evaluating Clostridium difficile adherence to differentiated intestinal Caco-2 cells

Dingle

Mulvey

Humphries

et al. 2010

Journal of Medical Microbiology

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Herein we describe a real-time quantitative PCR assay for evaluating the adherence of Clostridium difficile to differentiated human intestinal Caco-2 cells. Our investigations demonstrated that the method, employing the C. difficile-specific triose-phosphate isomerase gene, is as reliable but less time-consuming than counting c.f.u. We conclude that the method will be useful for evaluating the role of host cell adherence in the pathogenesis of C. difficile infection. INTRODUCTIONClostridium difficile is a Gram-positive anaerobic microorganism that is the most important cause of antibioticassociated diarrhoea, now generally referred to as C. difficile infection (CDI), in humans. To cause clinical illness, C. difficile first penetrates the mucus layer covering the epithelial surface of the gastrointestinal (GI) tract; a strategy that is most likely facilitated by flagella and proteases (Deneve et al., 2009;Tasteyre et al., 2001). Once established in the GI tract, C. difficile expresses two large exotoxins, toxin A (TcdA) and toxin B (TcdB) (Jank & Aktories, 2008;Voth & Ballard, 2005). Delivery of TcdA and TcdB to the cytoplasmic compartment of epithelial cells then leads to glucosylation of Rho family GTPases, resulting in disorganization of the host cell cytoskeleton (Deneve et al., 2009). This results in the loosening of tight junctions between adjacent intestinal epithelial cells ultimately leading to inflammation and diarrhoea.Although TcdA and TcdB represent primary virulence factors, whether adherence to host epithelial cells is also important in the C. difficile pathogenic strategy is less clear. However, C. difficile adherence to epithelial cells in vitro has been reported to be mediated by several colonization factors, including the low-and high-molecular-mass Slayer proteins which are derived by post-translational cleavage of the S-layer precursor protein, SlpA (Calabi et al., 2001). The high-molecular-mass S-layer protein is largely responsible for C. difficile binding to both human GI tissues and to components of the extracellular matrix (Calabi et al., 2002). In addition, Cwp84, a putative colonization factor and cysteine protease, has recently been implicated in a process whereby SlpA is cleaved into lowand high-molecular-mass counterparts (Janoir et al., 2007;Kirby et al., 2009). Several other cell-surface colonization factors including Cwp66, Fbp68 and GroEL, may also all play a role in C. difficile adherence to intestinal epithelial cells (Hennequin et al., , 2003Waligora et al., 2001). Moreover, the flagellar proteins FliC (flagellin) and FliD (flagellar cap protein) bind to axenic mouse mucus possibly facilitating the initial penetration of the intestinal mucus layer (Tasteyre et al., 2001). CDI patients are known to produce serum antibodies to one or more of these cellsurface proteins during infection, emphasizing their potential role in pathogenesis and generating a protective host immune response (Pechine et al., 2005;Wright et al., 2008).Several in vitro C. difficile adherence assays have be...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A real-time quantitative PCR assay for evaluating Clostridium difficile adherence to differentiated intestinal Caco-2 cells

Dingle

Mulvey

Humphries

et al. 2010

Journal of Medical Microbiology

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“…Durante el curso clínico de la IACD se ha observado un importante aumento de la cantidad de esporas excretadas por las deposiciones 2,70,71 , indicando que C. difficile esporula dentro del tracto intestinal, contribuyendo a la persistencia dentro del hospedero (Figura 2). La resistencia de las esporas de C. difficile a los antimicrobianos es tal, que éstas pueden persistir después de un curso terapéutico de metronidazol y vancomicina 72 .…”

Section: Factores De Persistencia De Las Esporas De C Difficile En Eunclassified

Esporas de Clostridium difficile y su relevancia en la persistencia y transmisión de la infección

Barra-Carrasco

Hernández-Rocha

Ibáñez

et al. 2014

Rev. chil. infectol.

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Clostridium difficile spores and its relevance in the persistence and transmission of the infection C. difficile is an anaerobic spore former pathogen and the most important etiologic agent of nosocomial and community acquired antibiotics associated diarrheas. C. difficile infections (CDI) are responsible for an elevated rate of morbidity in developed and developing countries. Although the major virulence factors responsible for clinical symptoms of CDI are the two toxins TcdA and TcdB, C. difficile spores are the main vehicle of infection, persistence and transmission of CDI. Recent work has unrevealed unique properties of C. difficile spores that make them remarkable morphotypes of persistence and transmission in the host, including their resistance to antibiotics, the host immune response and disinfectants. The present review summarizes relevant aspects of C. difficile spore biology that have major implications from a clinical and medical perspective.

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“…Clostridium difficile infection (CDI) is due to an alteration of microbiota homeostasis, following a long period of antibiotic therapy (6). Several intestinal complications could occur, such as recurrent CDI.…”

Section: Introductionmentioning

confidence: 99%

Culturomics: bacterial species isolated in 3 healthy donors for faecal microbiota transplantation in Clostridium difficile infection

et al. 2017

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SummaryBackground. Clostridium difficile infections are the main cause of nosocomial acquired diarrhea, because of prolonged antibiotic regimens. In the last years, mortality has increased due to recurrent infections caused by metronidazole and vancomicin resistant hypervirulent C. difficile strain 027. Faecal Microbiota Transplantation (FMT) is an infusion of faecal material obtained from healthy donors. This procedure reduces mortality in recurrent C. difficile infections (CDI). In this study we identified bacterial species obtained from donors' stool samples using culturomics.Materials and methods. Three donors were selected for FMT in three recipients affected by CDI. Faces obtained for FMT underwent culturomics, applying 17 different culture methods.Results and conclusions. Several different bacteria were isolated from donors. In two donors 4 potentially pathogenic bacteria were isolated; this suggests the use of culturomics for donors' screening or for selection of bacteria to infuse.

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New trends in Clostridium difficile virulence and pathogenesis

Cited by 177 publications

References 60 publications

A real-time quantitative PCR assay for evaluating Clostridium difficile adherence to differentiated intestinal Caco-2 cells

A real-time quantitative PCR assay for evaluating Clostridium difficile adherence to differentiated intestinal Caco-2 cells

Esporas de Clostridium difficile y su relevancia en la persistencia y transmisión de la infección

Culturomics: bacterial species isolated in 3 healthy donors for faecal microbiota transplantation in Clostridium difficile infection

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