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dc.creatorQuesada Gómez, Carlos
dc.creatorLópez Ureña, Diana
dc.creatorChumbler, Nicole
dc.creatorKroh, Heather K.
dc.creatorCastro Peña, Carolina
dc.creatorRodríguez Sánchez, César
dc.creatorOrozco Aguilar, Josué
dc.creatorGonzález Camacho, Sara María
dc.creatorRucavado Romero, Alexandra
dc.creatorGuzmán Verri, Caterina
dc.creatorLawley, Trevor D.
dc.creatorLacy, D. Borden
dc.creatorChaves Olarte, Esteban
dc.description.abstractClostridium difficile strains within the hypervirulent clade 2 are responsible for nosocomial outbreaks worldwide. The increased pathogenic potential of these strains has been attributed to several factors but is still poorly understood. During a C. difficile outbreak, a strain from this clade was found to induce a variant cytopathic effect (CPE), different from the canonical arborizing CPE. This strain (NAP1V) belongs to the NAP1 genotype but to a ribotype different from the epidemic NAP1/RT027 strain. NAP1V and NAP1 share some properties, including the overproduction of toxins, the binary toxin, and mutations in tcdC. NAP1V is not resistant to fluoroquinolones, however. A comparative analysis of TcdB proteins from NAP1/RT027 and NAP1V strains indicated that both target Rac, Cdc42, Rap, and R-Ras but only the former glucosylates RhoA. Thus, TcdB from hypervirulent clade 2 strains possesses an extended substrate profile, and RhoA is crucial for the type of CPE induced. Sequence comparison and structural modeling revealed that TcdBNAP1 and TcdBNAP1V share the receptor-binding and autoprocessing activities but vary in the glucosyltransferase domain, consistent with the different substrate profile. Whereas the two toxins displayed identical cytotoxic potencies, TcdBNAP1 induced a stronger proinflammatory response than TcdBNAP1V as determined in ex vivo experiments and animal models. Since immune activation at the level of intestinal mucosa is a hallmark of C. difficile-induced infections, we propose that the panel of substrates targeted by TcdB is a determining factor in the pathogenesis of this pathogen and in the differential virulence potential seen among C. difficile strains.es_ES
dc.description.sponsorshipWellcome Trust, United States a Trevor D Lawley bajo el número 098051es_ES
dc.description.sponsorshipConsejo Nacional de Rectores/[803-B1-654]/CONARE/Costa Ricaes_ES
dc.description.sponsorshipConsejo Nacional de Rectores/[803-B4-652]/CONARE/Costa Ricaes_ES
dc.description.sponsorshipUniversidad de Costa Rica/[803-B5-107]/UCR/Costa Ricaes_ES
dc.description.sponsorshipUniversidad de Costa Rica/[803-B5-108]/UCR/Costa Ricaes_ES
dc.description.sponsorshipConsejo Nacional para Investigaciones Científicas y Tecnológicas/[FV-0004-13. HHS]/CONICIT/Costa Ricaes_ES
dc.description.sponsorshipNational Institutes of Health/[R01AI095755]/NIH/Estados Unidoses_ES
dc.rightsAtribución 3.0 Costa Rica*
dc.sourceInfection and Immunity; Volumen 84, Número 3, 856-865es_ES
dc.subjectClostridium difficilees_ES
dc.titleAnalysis of TcdB Proteins within the Hypervirulent Clade 2 Reveals an Impact of RhoA Glucosylation on Clostridium difficile Proinflammatory Activitieses_ES
dc.typeArtículo científicoes_ES
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)es_ES

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Atribución 3.0 Costa Rica
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