Abstract
Campylobacter concisus is an emerging pathogen associated with inflammatory bowel disease (IBD), yet little is known about the genetic diversity of C. concisus in relation to host niches and disease. We isolated 104 C. concisus isolates from saliva, mucosal biopsies and faecal samples from 41 individuals (26 IBD, 3 Gastroenteritis (GE), 12 Healthy controls (HC)). Whole genomes were sequenced and the dataset pan-genome examined, and genomic information was used for typing using multi-locus-sequence typing (MLST). C. concisus isolates clustered into two main groups/genomospecies (GS) with 71 distinct sequence types (STs) represented. Sampling site (p < 0.001), rather than disease phenotype (p = 1.00) was associated with particular GS. We identified 97 candidate genes associated with increase or decrease in prevalence during the anatomical descent from the oral cavity to mucosal biopsies to faeces. Genes related to cell wall/membrane biogenesis were more common in oral isolates, whereas genes involved in cell transport, metabolism and secretory pathways were more prevalent in enteric isolates. Furthermore, there was no correlation between individual genetic diversity and clinical phenotype. This study confirms the genetic heterogeneity of C. concisus and provides evidence that genomic variation is related to the source of isolation, but not clinical phenotype.
Highlights
Campylobacter concisus is an emerging pathogen that is a part of the commensal human oral microbiota[1]
When annotated according to disease status, there was no difference between GS, as isolates deriving from inflammatory bowel disease (IBD) patients, diarrheic patients and healthy controls were present in both clusters (p = 1.00) (Fig. 1A)
We present analyses of 104 C. concisus isolates from both IBD patients and healthy controls, including samples collected from different anatomical sites in the same individual
Summary
Campylobacter concisus is an emerging pathogen that is a part of the commensal human oral microbiota[1]. One of the advantages of MLST is that sequence data can be exchanged between laboratories for use in global epidemiological research These studies have shown a consistent division of C. concisus isolates into two main clusters or genomospecies (GS), regardless of typing method. Phylogenetic differentiation has been reported among isolates from gastroenteritis and Crohn’s disease, implying genetic differences associated with diseasephenotypes[9] These studies provide a good basis for considering the molecular epidemiology of C. consisus but further work, with large well characterised isolate collections, is necessary to understand how population structure relates to clinical significance in these highly diverse, recombining bacteria[15]. In this study we investigated oral, gut mucosal and faecal isolates sampled from patients with inflammatory bowel disease (IBD), diarrhoae/gastroenteritis (GE), and healthy controls (HC). We used MLST, whole genome sequencing, core- and accessory genome characterization to investigate the diversity of a large number of isolates from different anatomical sites within individuals, including gut mucosal biopsies from healthy controls
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