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

作者：Costa Cecilia Leite; Lopez Urena Diana; Assis Thiago de Oliveira; Ribeiro Ronaldo A; Silveira Silva Rodrigo Otavio; Rupnik Maja; Wilcox Mark H; de Carvalho Alex Fiorini; do Carmo Anderson Oliveira; Martins Dias Adriana Abalen; Mano de Carvalho Cibele Barreto; Chaves Olarte Esteban; Rodriguez Cesar; Quesada Gomez Carlos^*; de Castro Brito Gerly Anne

来源：Anaerobe, 2016, 40: 76-84.

DOI：10.1016/j.anaerobe.2016.06.005

• Clostridium difficile
• MLST Clade 2
• Variant toxin B
• Inflammation
• Oxidative stress response

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.

• 出版日期2016-8