Whole genome comparison of Campylobacter jejuni human isolates using a low-cost microarray reveals extensive genetic diversity

Abstract

Campylobacter jejuni is the leading cause of bacterial food-borne diarrhoeal disease throughout the world, and yet is still a poorly understood pathogen. Whole genome microarray comparisons of 11 C. jejuni strains of diverse origin identified genes in up to 30 NCTC 11168 loci ranging from 0.7 to 18.7 kb that are either absent or highly divergent in these isolates. Many of these regions are associated with the biosynthesis of surface structures including flagella, lipo-oligosaccharide, and the newly identified capsule. Other strain-variable genes of known function include those responsible for iron acquisition, DNA restriction/modification, and sialylation. In fact, at least 21% of genes in the sequenced strain appear dispensable as they are absent or highly divergent in one or more of the isolates tested, thus defining 1300 C. jejuni core genes. Such core genes contribute mainly to metabolic, biosynthetic, cellular, and regulatory processes, but many virulence determinants are also conserved. Comparison of the capsule biosynthesis locus revealed conservation of all the genes in this region in strains with the same Penner serotype as strain NCTC 11168. By contrast, between 5 and 17 NCTC 11168 genes in this region are either absent or highly divergent in strains of a different serotype from the sequenced strain, providing further evidence that the capsule accounts for Penner serotype specificity. These studies reveal extensive genetic diversity among C. jejuni strains and pave the way toward identifying correlates of pathogenicity and developing improved epidemiological tools for this problematic pathogen.

Figure 1

Comparison of the genomes of 11 different Campylobacter jejuni strains with the NCTC 11168 genome. Genes identified as absent by microarray hybridization analysis are indicated as a vertical line depicting the position of the gene in a linear representation of the 1.64-Mb NCTC 11168 genome from Cj0001to Cj1654. Lines above the horizontal line indicate genes on the forward strand, and lines below indicate genes on the reverse strand. (LOS) Lipo-oligosaccharide biosynthesis locus, (FM) flagellar modification locus, and (CAP) capsule biosynthesis locus.

Figure 2

Cluster analysis performed using GeneSpring 3.2.12 software showing the relationship of all 11 Campylobacter jejuni strains studied to each other based on their genomic composition compared to the sequenced strain NCTC 11168.