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 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.
Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Laboratory of Bacteriology, Department of Pathology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Cecília Leite
CL
Costa
Facultad de Microbiología and Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, San José, Costa Rica.
Diana
D
López-Ureña
Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Morphology, Federal University of Paraíba, João Pessoa, PB, Brazil.
Thiago
T
de Oliveira Assis
Haroldo Juaçaba Hospital, Cancer Institute of Ceará, Fortaleza, CE, Brazil; Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
Ronaldo A
RA
Ribeiro
Veterinary School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Rodrigo Otávio Silveira
RO
Silva
University of Maribor, Faculty of Medicine and National Laboratory for Health, Environment and Food, Maribor, Slovenia.
Maja
M
Rupnik
Department of Microbiology, Leeds Teaching Hospitals NHS Trust, The General Infirmary, Leeds, UK.
Mark H
MH
Wilcox
Experimental Genetics and Laboratory Animal Science, Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Alex Fiorini
AF
de Carvalho
Experimental Genetics and Laboratory Animal Science, Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Anderson Oliveira
AO
do Carmo
Experimental Genetics and Laboratory Animal Science, Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Adriana Abalen Martins
AA
Dias
Laboratory of Bacteriology, Department of Pathology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Cibele Barreto Mano
CB
de Carvalho
Facultad de Microbiología and Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, San José, Costa Rica.
Esteban
E
Chaves-Olarte
Facultad de Microbiología and Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, San José, Costa Rica.
César
C
Rodríguez
Facultad de Microbiología and Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, San José, Costa Rica. Electronic address: carlos.quesada@ucr.ac.cr.
Carlos
C
Quesada-Gómez
Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: gerlybrito@hotmail.com.
Gerly Anne
GA
de Castro Brito
D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D016360:Clostridioides difficile / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D003967:Diarrhea / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D058885:Multilocus Sequence Typing; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D018384:Oxidative Stress; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D021521:Ribotyping
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile
Clostridium difficile; Inflammation; MLST Clade 2; Oxidative stress response; Variant toxin B