Genetic import and phenotype specific alleles associated with hyper-invasion in Campylobacter jejuni.
BACKGROUND
Campylobacter jejuni is a major zoonotic pathogen, causing gastroenteritis in humans. Invasion is an important pathogenesis trait by which C. jejuni causes disease. Here we report the genomic analysis of 134 strains to identify traits unique to hyperinvasive isolates.


METHODS
A total of 134 C. jejuni genomes were used to create a phylogenetic tree to position the hyperinvasive strains. Comparative genomics lead to the identification of mosaic capsule regions. A pan genome approach led to the discovery of unique loci, or loci with unique alleles, to the hyperinvasive strains.


RESULTS
Phylogenetic analysis showed that the hyper-invasive phenotype is a generalist trait. Despite the fact that hyperinvasive strains are only distantly related based on the whole genome phylogeny, they all possess genes within the capsule region with high identity to capsule genes from C. jejuni subsp. doylei and C. lari. In addition there were genes unique to the hyper-invasive strains with identity to non-C. jejuni genes, as well as allelic variants of mainly pathogenesis related genes already known in the other C. jejuni. In particular, the sequence of flagella genes, flgD-E and flgL were highly conserved amongst the hyper-invasive strains and divergent from sequences in other C. jejuni. A novel cytolethal distending toxin (cdt) operon was also identified as present in all hyper-invasive strains in addition to the classic cdt operon present in other C. jejuni.


CONCLUSIONS
Overall, the hyper-invasive phenotype is strongly linked to the presence of orthologous genes from other Campylobacter species in their genomes, notably within the capsule region, in addition to the observed association with unique allelic variants in flagellar genes and the secondary cdt operon which is unlikely under random sharing of accessory alleles in separate lineages.
School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK. abiyad.baig@yahoo.com.|Department of Veterinary Medicine, University of Cambridge, Cambridge, UK. abiyad.baig@yahoo.com.
Abiyad
A
Baig
School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK. alan.mcnally@ntu.ac.uk.
Alan
A
McNally
School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK. steven.dunn2010@my.ntu.ac.uk.
Steven
S
Dunn
Wellcome Trust Biomedical Informatics Hub, University of Exeter, Exeter, UK. K.h.paszkiewicz@exeter.ac.uk.
Konrad H
KH
Paszkiewicz
Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland. Jukka.corander@helsinki.fi.
Jukka
J
Corander
School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK. georgina.manning@ntu.ac.uk.
Georgina
G
Manning
D000483:Alleles; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism; D002169:Campylobacter Infections / Q000382:microbiology; D016123:Campylobacter jejuni / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D023061:Gene Order; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D006801:Humans; D010641:Phenotype; D010802:Phylogeny; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D040641:Quantitative Trait Loci
D011135:Polysaccharides, Bacterial