Genomic analysis of oral Campylobacter concisus strains identified a potential bacterial molecular marker associated with active Crohn's disease.
Fang Liu, Rena Ma, Chin Yen Alfred Tay, Sophie Octavia, Ruiting Lan, Heung Kit Leslie Chung, Stephen M Riordan, Michael C Grimm, Rupert W Leong, Mark M Tanaka, Susan Connor, Li Zhang
Author Information
Fang Liu: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Rena Ma: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Chin Yen Alfred Tay: Helicobacter Research Laboratory, Marshall Centre for Infectious Diseases Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
Sophie Octavia: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Ruiting Lan: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Heung Kit Leslie Chung: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Stephen M Riordan: Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia.
Michael C Grimm: St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia.
Rupert W Leong: Concord Hospital, University of New South Wales, Sydney, NSW, Australia.
Mark M Tanaka: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Susan Connor: Liverpool Hospital, University of New South Wales, Sydney, NSW, Australia.
Li Zhang: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia. L.Zhang@unsw.edu.au.
Campylobacter concisus is an oral bacterium that is associated with inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC). C. concisus consists of two genomospecies (GS) and diverse strains. This study aimed to identify molecular markers to differentiate commensal and IBD-associated C. concisus strains. The genomes of 63 oral C. concisus strains isolated from patients with IBD and healthy controls were examined, of which 38 genomes were sequenced in this study. We identified a novel secreted enterotoxin B homologue, Csep1. The csep1 gene was found in 56% of GS2 C. concisus strains, presented in the plasmid pICON or the chromosome. A six-nucleotide insertion at the position 654-659 bp in csep1 (csep1-6bpi) was found. The presence of csep1-6bpi in oral C. concisus strains isolated from patients with active CD (47%, 7/15) was significantly higher than that in strains from healthy controls (0/29, P = 0.0002), and the prevalence of csep1-6bpi positive C. concisus strains was significantly higher in patients with active CD (67%, 4/6) as compared to healthy controls (0/23, P = 0.0006). Proteomics analysis detected the Csep1 protein. A csep1 gene hot spot in the chromosome of different C. concisus strains was found. The pICON plasmid was only found in GS2 strains isolated from the two relapsed CD patients with small bowel complications. This study reports a C. concisus molecular marker (csep1-6bpi) that is associated with active CD.
