A MLST Clade 2 Clostridium difficile strain with a variant TcdB induces severe inflammatory and oxidative response associated with mucosal disruption

The epidemiology of Clostridium difficile infections is highly dynamic as new strains continue to emerge worldwide. Here we present a detailed analysis of a new C. difficile strain (ICC-45) recovered from a cancer patient in Brazil that died from severe diarrhea. A polyphasic approach assigned a new...

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Main Authors: Leite Costa, Cecília, López Ureña, Diana, de Oliveira Assis, Thiago, Ribeiro, Ronaldo A., Silveira Silva, Rodrigo Otavio, Rupnik, Maja, Wilcox, Mark H., Fiorini de Carvalho, Alex, Oliveira do Carmo, Anderson, Abalen Martins Dias, Adriana, Barreto Mano de Carvalho, Cibele, Chaves Olarte, Esteban, Rodríguez Sánchez, César, Quesada Gómez, Carlos, de Castro Brito, Gerly Anne
Format: artículo científico
Language: Inglés
Published: 2017
Subjects:
Online Access: http://www.sciencedirect.com/science/article/pii/S1075996416300737
https://hdl.handle.net/10669/30377
Summary: The epidemiology of Clostridium difficile infections is highly dynamic as new strains continue to emerge worldwide. Here we present a detailed analysis of a new C. difficile strain (ICC-45) recovered from a cancer patient in Brazil that died from severe diarrhea. A polyphasic approach assigned a new PCR-ribotype and PFGE macrorestriction pattern to strain ICC-45, which is toxigenic (tcdA+, tcdB+ and ctdB+) and classified as ST41 from MLST Clade 2 and toxinotype IXb. Strain ICC-45 encodes for a variant TcdB that induces a distinct CPE in agreement with its toxinotype. Unlike epidemic NAP1/027 strains, which are also classified to MLST Clade 2, strain ICC-45 is susceptible to fluoroquinolones and does not overproduce toxins TcdA and TcdB. However, supernatants from strain ICC-45 and a NAP1/027 strain produced similar expression of pro-inflammatory cytokines, epithelial damage, and oxidative stress response in the mouse ileal loop model. These results highlight inflammation and oxidative stress as common features in the pathogenesis of C. difficile Clade 2 strains. Finally, this work contributes to the description of differences in virulence among various C. difficile strains.