Comparative genomics of Campylobacter concisus isolates reveals genetic diversity and provides insights into disease association

Nandan P Deshpande,Nadeem O Kaakoush,Marc R Wilkins,Hazel M Mitchell

doi:10.1186/1471-2164-14-585

Abstract

BackgroundIn spite of its association with gastroenteritis and inflammatory bowel diseases, the isolation of Campylobacter concisus from both diseased and healthy individuals has led to controversy regarding its role as an intestinal pathogen. One proposed reason for this is the presence of high genetic diversity among the genomes of C. concisus strains.ResultsIn this study the genomes of six C. concisus strains were sequenced, assembled and annotated including two strains isolated from Crohn’s disease patients (UNSW2 and UNSW3), three from gastroenteritis patients (UNSW1, UNSWCS and ATCC 51562) and one from a healthy individual (ATCC 51561). The genomes of C. concisus BAA-1457 and UNSWCD, available from NCBI, were included in subsequent comparative genomic analyses. The Pan and Core genomes for the sequenced C. concisus strains consisted of 3254 and 1556 protein coding genes, respectively.ConclusionGenes were identified with specific conservation in C. concisus strains grouped by phenotypes such as invasiveness, adherence, motility and diseased states. Phylogenetic trees based on ribosomal RNA sequences and concatenated host-related pathways for the eight C. concisus strains were generated using the neighbor-joining method, of which the 16S rRNA gene and peptidoglycan biosynthesis grouped the C. concisus strains according to their pathogenic phenotypes. Furthermore, 25 non-synonymous amino acid changes with 14 affecting functional domains, were identified within proteins of conserved host-related pathways, which had possible associations with the pathogenic potential of C. concisus strains. Finally, the genomes of the eight C. concisus strains were compared to the nine available genomes of the well-established pathogen Campylobacter jejuni, which identified several important differences in the respiration pathways of these two species. Our findings indicate that C. concisus strains are genetically diverse, and suggest the genomes of this bacterium contain respiration pathways and modifications in the peptidoglycan layer that may play an important role in its virulence.

Highlights

In spite of its association with gastroenteritis and inflammatory bowel diseases, the isolation of Campylobacter concisus from both diseased and healthy individuals has led to controversy regarding its role as an intestinal pathogen
Investigation of the pathogenic potential of C. concisus strains has shown that the bacterium can adhere to human intestinal epithelial cells, only some can invade into the cells through transcellular and paracellular mechanisms [13,14]
Draft genome assemblies and plasmids of six Campylobacter concisus strains Genomic read-data for the six C. concisus strains was generated using a multiplexing approach in a single lane on an Illumina HiSeq sequencing platform, and de novo assemblies with varying contig numbers ranging from 28–207 (9–53 scaffolds) were obtained

Summary

Introduction

In spite of its association with gastroenteritis and inflammatory bowel diseases, the isolation of Campylobacter concisus from both diseased and healthy individuals has led to controversy regarding its role as an intestinal pathogen. Based on a C. concisus-specific PCR, a significantly higher prevalence of C. concisus DNA was shown to be present in both biopsy and faecal samples of children with newly diagnosed CD than in controls [9,10]. Host cells infected with C. concisus were found to produce high amounts of IL-12, only C. concisus strains capable of internalising into host cells induced a significantly increased quantity of IFN-γ with respect to controls [13]. These findings, coupled with the regulation of the proteasome, ubiquitination pathways, the Akt signalling pathway and NF-κB inhibitors, pointed towards the activation of the NF-κB pathway by invasive C. concisus strains [13]. Further investigation of the difference in invasive potential between strains identified a plasmid containing several virulence determinants, including exotoxin 9 [13,15], which was present in the highly invasive strains but absent in the other strains

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Conclusion