Comparative genomics and genome biology of Campylobacter showae

Authors: HSU, TIFFANY - Harvard School Of Public Health; GEMMELL, MATTHEW - University Of Aberdeen; FRANZOSA, ERIC - Harvard School Of Public Health; BERRY, SUSAN - University Of Aberdeen; MUKHOPADHYA, INDRANI - University Of Aberdeen; HANSEN, RICHARD - University Of Aberdeen; MICHAUD, MONIA - Harvard School Of Public Health; NIELSEN, HANS - Aalborg University Hospital; Miller, William - Bill; NIELSEN, HENRIK - Aalborg University Hospital; BAJAJ-ELLIOTT, MONA - University College London; HUTTENHOWER, CURTIS - Harvard School Of Public Health; GARRETT, WENDY - Harvard School Of Public Health; HOLD, GEORGINA - University Of Aberdeen

Submitted to: Emerging Microbes & Infections
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2019
Publication Date: 6/6/2019
Citation: Hsu, T., Gemmell, M.R., Franzosa, E., Berry, S., Mukhopadhya, I., Hansen, R., Michaud, M., Nielsen, H., Miller, W.G., Nielsen, H., Bajaj-Elliott, M., Huttenhower, C., Garrett, W.S., Hold, G.L. 2019. Comparative genomics and genome biology of Campylobacter showae. Emerging Microbes & Infections. 8(1):827-840. https://doi.org/10.1080/22221751.2019.1622455.
DOI: https://doi.org/10.1080/22221751.2019.1622455

Interpretive Summary: Campylobacter species are generally associated with human gastroenteritis. However, some species are more prevalent in oral environments and are often isolated from human patients with gum disease. One such species is Campylobacter showae. Although isolated from the human mouth, C. showae strains in recent years have been isolated from patients with serious gastrointestinal issues, such as inflammatory bowel disease, ulcerative colitis and colorectal cancer, thus implicating C. showae in the development of these diseases. To understand the potential genetic differences between C. showae isolated from oral environments and those from patients with serious bowel disease, the chromosomal DNA sequences of eight gastrointestinal strains were compared with those from oral-derived strains. Analysis of these sequences indicated a clear difference between the two sets. Gut-associated strains contained mechanisms for exporting proteins out of the cell and possessed genes that could lead to a unique outer surface structure. These strains also lacked defense mechanisms that typically guard against viruses in bacteria. Taken together, the data suggest that the genetic differences between the two sets of strains may lead to differences in the pathology of C. showae and the potential development of serious gastrointestinal illness.

Technical Abstract: In recent years, an increasing number of Campylobacter species have been associated with human gastrointestinal diseases. Campylobacter showae, an oral commensal that was historically linked to gingivitis and periodontitis, has recently been associated with newly diagnosed and established inflammatory bowel disease, hepatolithiasis, and colorectal cancer. Our aim was to generate robust genome sequence data for a number of clinical C. showae strains and identify functional properties that could explain their pathogenic potential. Genomes of eight C. showae strains were sequenced, assembled, annotated, and compared including four strains from paediatric Crohn’s disease patients, three strains from colonic adenomas and one from a patient with gastroenteritis. The 8 new genome assemblies were of high contiguity and completeness and were subsequently analysed alongside the existing 3 C. showae genomes. The pangenome from these 11 strains consisted of 4,799 unique protein families, and the core genome size was estimated at 1050 +/- 14.33 genes with each new genome contributing an additional 206 +/- 15.59 genes. Functional assays indicated that colonic strains can be classified into 2 groups - adherent/invasive vs non-adherent/non-invasive strains. The former possessed Type IV secretion machinery and S-layer proteins that were absent in non-adherent strains, while the latter contained CRISPR enzymes. Comparison of the isolates’ gene profiles with those from the Human Microbiome Project oral metagenomes showed that these gut-derived isolates share genes specific to their tongue dorsum or supragingival plaque counterparts. These differences may contribute to the distinct phenotypes we observed between strains relating to motility, metal ion transport and host cell interaction. Our findings indicate that C. showae strains are phenotypically and genetically diverse and suggest that presence/absence in secretion systems may play an important role in their virulence potential.