Comparative phylogenomics of the food-borne pathogen Campylobacter jejuni reveals genetic markers predictive of infection source

Abstract

Campylobacter jejuni is the predominant cause of bacterial gastroenteritis worldwide, but traditional typing methods are unable to discriminate strains from different sources that cause disease in humans. We report the use of genomotyping (whole-genome comparisons of microbes using DNA microarrays) combined with Bayesian-based algorithms to model the phylogeny of this major food-borne pathogen. In this study 111 C. jejuni strains were examined by genomotyping isolates from humans with a spectrum of C. jejuni-associated disease (70 strains), chickens (17 strains), bovines (13 strains), ovines (5 strains), and the environment (6 strains). From these data, the Bayesian phylogeny of the isolates revealed two distinct clades unequivocally supported by Bayesian probabilities (P ‫؍‬ 1); a livestock clade comprising 31͞35 (88.6%) of the livestock isolates and a ''nonlivestock'' clade comprising further clades of environmental isolates. Several genes were identified as characteristic of strains in the livestock clade. The most prominent was a cluster of six genes (cj1321 to cj1326) within the flagellin glycosylation locus, which were confirmed by PCR analysis as genetic markers in six additional chicken-associated strains. Surprisingly these studies show that the majority (39͞70, 55.7%) of C. jejuni human isolates were found in the nonlivestock clade, suggesting that most C. jejuni infections may be from nonlivestock (and possibly nonagricultural) sources. This study has provided insight into a previously unidentified reservoir of C. jejuni infection that may have implications in disease-control strategies. The comparative phylogenomics approach described provides a robust methodological prototype that should be applicable to other microbes. microarray analysis ͉ gastrointestinal pathogen ͉ Bayesian-based algorithm

Flagellar glycosylation – a new component of the motility repertoire?

“…Campylobacter isolates display significant genetic diversity within this locus, which has been shown to be responsible for the antigenically distinct PseAm glycan variants produced by individual strains (Logan et al, 2002). Most recently, comparative phylogenomics revealed a cluster of six genes within this locus to be a specific marker for a 'livestock' clade (Champion et al, 2005), although the role of these genes in production of a unique glycoform relevant to adhesion in the livestock gut has yet to be demonstrated. The annotation of the locus suggested that approximately 50 % of the genes were likely to be involved in carbohydrate biosynthetic pathways and that some of them had homology to sialic acid biosynthesis genes (neuA, neuB, neuC).…”

Lack of Association between the Presence of the pVir Plasmid and Bloody Diarrhea in Campylobacter jejuni Enteritis

“…The absence of an association between the presence of pVir and bloody stools suggests that other virulence factors may be involved in the development of bloody diarrhea. A suggestion in this direction was recently made by Champion et al (2), who proposed a serine protease encoded by Cj1365 as a virulence factor involved in the development of bloody diarrhea. Previously, serine proteases have been described in Enterobacteriaceae and are thought to be involved in the development of bloody diarrhea caused by Escherichia coli (4).…”

Genetic and molecular analyses reveal an evolutionary trajectory for glycan synthesis in a bacterial protein glycosylation system

“…Some systems display robust inter-and intrastrain glycan variability, suggesting that glycoform diversification is adaptive. For example, flagellar protein glycosylation systems in Campylobacter jejuni and Clostridium species display remarkable plasticity in glycoform expression (2)(3)(4). However, precise correlations between glycosylation gene content and glycoform phenotypes have been difficult to establish.…”