Emergence of an outbreak-associated Clostridium difficile variant with increased virulence

The prevalence of Clostridium difficile infections has increased due to the emergence of epidemic variants from diverse genetic lineages. Here we describe the emergence of a novel variant during an outbreak in a Costa Rican hospital that was associated with severe clinical presentations. This C. dif...

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Autores Principales: Guzman-Verri, Caterina, Quesada-Gómez, Carlos, López-Ureña, Diana, Acuña-Amador, Luis, Villalobos-Zúñiga, Manuel, Du, Tim, Freire, Rosemayre, Gamboa-Coronado, María del Mar, Lawley, Trevor, Moreno, Edgardo, Mulvey, Michael, de Castro Brito, Gerly Anne, Rodríguez-Cavallini, Evelyn, Rodríguez, César, Chaves-Olarte, Esteban
Formato: Artículo
Idioma: Inglés
Publicado: Journal of Clinical Microbiology 2020
Materias:
PCR
Acceso en línea: http://hdl.handle.net/11056/17641
id RepoUNACR17641
recordtype dspace
spelling RepoUNACR176412020-10-06T20:46:10Z Emergence of an outbreak-associated Clostridium difficile variant with increased virulence Guzman-Verri, Caterina Quesada-Gómez, Carlos López-Ureña, Diana Acuña-Amador, Luis Villalobos-Zúñiga, Manuel Du, Tim Freire, Rosemayre Gamboa-Coronado, María del Mar Lawley, Trevor Moreno, Edgardo Mulvey, Michael de Castro Brito, Gerly Anne Rodríguez-Cavallini, Evelyn Rodríguez, César Chaves-Olarte, Esteban CLOSTRIDIUM DIFFICILE PREVALENCE ENFERMEDADES INFECCIOSAS PCR The prevalence of Clostridium difficile infections has increased due to the emergence of epidemic variants from diverse genetic lineages. Here we describe the emergence of a novel variant during an outbreak in a Costa Rican hospital that was associated with severe clinical presentations. This C. difficile variant elicited higher white blood cell counts and caused disease in younger patients than did other strains isolated during the outbreak. Furthermore, it had a recurrence rate, a 30-day attributable disease rate, and disease severity as great as those of the epidemic strain NAP1. Pulsed-field gel electrophoresis genotyping indicated that the outbreak strains belong to a previously undescribed variant, designated NAPCR1. Whole-genome sequencing and ribotyping indicated that the NAPCR1 variant belongs to C. difficile ribotype 012 and sequence type 54, as does the reference strain 630. NAPCR1 strains are resistant to fluoroquinolones due to a mutation in gyrA, and they possess an 18-bp deletion in tcdC that is characteristic of the epidemic, evolutionarily distinct, C. difficile NAP1 variant. NAPCR1 genomes contain 10% more predicted genes than strain 630, most of which are of hypothetical function and are present on phages and other mobile genetic elements. The increased virulence of NAPCR1 was confirmed by mortality rates in the hamster model and strong inflammatory responses induced by bacteria-free supernatants in the murine ligated loop model. However, NAPCR1 strains do not synthesize toxin A and toxin B at levels comparable to those in NAP1 strains. Our results suggest that the pathogenic potential of this emerging C. difficile variant is due to the acquisition of hypothetical functions associated with laterally acquired DNA. La prevalencia de las infecciones por Clostridium difficile ha aumentado debido a la aparición de variantes epidémicas de diversos linajes genéticos. Aquí describimos la aparición de una nueva variante durante un brote en un hospital costarricense que se asoció con presentaciones clínicas graves. Esta variante de C. difficile provocó un mayor recuento de glóbulos blancos y causó la enfermedad en pacientes más jóvenes que otras cepas aisladas durante el brote. Además, tenía una tasa de recurrencia, una tasa de enfermedad atribuible a 30 días y una gravedad de la enfermedad tan grande como las de la cepa epidémica NAP1. El genotipo de electroforesis en gel de campo pulsado indicó que las cepas del brote pertenecen a una variante no descrita anteriormente, designada NAPCR1. La secuenciación del genoma completo y el ribotipado indicaron que la variante NAPCR1 pertenece al ribotipo 012 de C. difficile y al tipo de secuencia 54, al igual que la cepa de referencia 630. Las cepas NAPCR1 son resistentes a las fluoroquinolonas debido a una mutación en gyrA, y poseen una deleción de 18 pb en tcdC que es característica de la epidemia, evolutivamente distinta, variante NAP1 de C. difficile. Los genomas de la NAPCR1 contienen un 10% más de genes predichos que la cepa 630, la mayoría de los cuales tienen una función hipotética y están presentes en los fagos y otros elementos genéticos móviles. El aumento de la virulencia de la NAPCR1 fue confirmado por las tasas de mortalidad en el modelo del hámster y las fuertes respuestas inflamatorias inducidas por sobrenadantes libres de bacterias en el modelo de bucle ligado murino. Sin embargo, las cepas de la NAPCR1 no sintetizan la toxina A y la toxina B a niveles comparables a los de las cepas de la NAP1. Nuestros resultados sugieren que el potencial patógeno de esta variante emergente de C. difficile se debe a la adquisición de hipotéticas funciones asociadas al ADN adquirido lateralmente. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria 2020-06-23T21:58:10Z 2020-06-23T21:58:10Z 2015-04-23 http://purl.org/coar/resource_type/c_6501 http://hdl.handle.net/11056/17641 10.1128/JCM.03058-14 eng Acceso abierto http://creativecommons.org/licenses/by-nc-nd/3.0/ application/pdf Journal of Clinical Microbiology J Clin Microbiol Vol. 53 No. 4: 1216–1226 April 2015
institution Universidad Nacional de Costa Rica
collection Repositorio UNA-Costa Rica
language Inglés
topic CLOSTRIDIUM DIFFICILE
PREVALENCE
ENFERMEDADES INFECCIOSAS
PCR
spellingShingle CLOSTRIDIUM DIFFICILE
PREVALENCE
ENFERMEDADES INFECCIOSAS
PCR
Guzman-Verri, Caterina
Quesada-Gómez, Carlos
López-Ureña, Diana
Acuña-Amador, Luis
Villalobos-Zúñiga, Manuel
Du, Tim
Freire, Rosemayre
Gamboa-Coronado, María del Mar
Lawley, Trevor
Moreno, Edgardo
Mulvey, Michael
de Castro Brito, Gerly Anne
Rodríguez-Cavallini, Evelyn
Rodríguez, César
Chaves-Olarte, Esteban
Emergence of an outbreak-associated Clostridium difficile variant with increased virulence
description The prevalence of Clostridium difficile infections has increased due to the emergence of epidemic variants from diverse genetic lineages. Here we describe the emergence of a novel variant during an outbreak in a Costa Rican hospital that was associated with severe clinical presentations. This C. difficile variant elicited higher white blood cell counts and caused disease in younger patients than did other strains isolated during the outbreak. Furthermore, it had a recurrence rate, a 30-day attributable disease rate, and disease severity as great as those of the epidemic strain NAP1. Pulsed-field gel electrophoresis genotyping indicated that the outbreak strains belong to a previously undescribed variant, designated NAPCR1. Whole-genome sequencing and ribotyping indicated that the NAPCR1 variant belongs to C. difficile ribotype 012 and sequence type 54, as does the reference strain 630. NAPCR1 strains are resistant to fluoroquinolones due to a mutation in gyrA, and they possess an 18-bp deletion in tcdC that is characteristic of the epidemic, evolutionarily distinct, C. difficile NAP1 variant. NAPCR1 genomes contain 10% more predicted genes than strain 630, most of which are of hypothetical function and are present on phages and other mobile genetic elements. The increased virulence of NAPCR1 was confirmed by mortality rates in the hamster model and strong inflammatory responses induced by bacteria-free supernatants in the murine ligated loop model. However, NAPCR1 strains do not synthesize toxin A and toxin B at levels comparable to those in NAP1 strains. Our results suggest that the pathogenic potential of this emerging C. difficile variant is due to the acquisition of hypothetical functions associated with laterally acquired DNA.
format Artículo
author Guzman-Verri, Caterina
Quesada-Gómez, Carlos
López-Ureña, Diana
Acuña-Amador, Luis
Villalobos-Zúñiga, Manuel
Du, Tim
Freire, Rosemayre
Gamboa-Coronado, María del Mar
Lawley, Trevor
Moreno, Edgardo
Mulvey, Michael
de Castro Brito, Gerly Anne
Rodríguez-Cavallini, Evelyn
Rodríguez, César
Chaves-Olarte, Esteban
author_sort Guzman-Verri, Caterina
title Emergence of an outbreak-associated Clostridium difficile variant with increased virulence
title_short Emergence of an outbreak-associated Clostridium difficile variant with increased virulence
title_full Emergence of an outbreak-associated Clostridium difficile variant with increased virulence
title_fullStr Emergence of an outbreak-associated Clostridium difficile variant with increased virulence
title_full_unstemmed Emergence of an outbreak-associated Clostridium difficile variant with increased virulence
title_sort emergence of an outbreak-associated clostridium difficile variant with increased virulence
publisher Journal of Clinical Microbiology
publishDate 2020
url http://hdl.handle.net/11056/17641
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score 12.140644