Understanding Campylobacter jejuni genomic diversity

Campylobacter jejuni Campylobacter jejuni, a Gram-negative bacterium, is one of the leading bacterial causes of food-borne human gastroenteritis. C. jejuni is currently estimated to cause 5–14% of diarrhoea worldwide, which translates into 400–500 million cases per year. Most cases of C. jejuni mediated gastroenteritis (campylobacteriosis) are characterized by nausea, abdominal cramps, diarrhea, and fatigue. While outbreaks of campylobacteriosis occur predominantly through consumption of contaminated milk and untreated water, most Campylobacter infections are sporadic in nature and linked to the improper handling and consumption of poultry. The linkage between human infection and the handling of raw poultry is not unexpected, as C. jejuni is a common commensal organism of chickens. In fact, C. jejuni colonize the intestinal tract of a variety of animals, including common livestock (cattle, sheep, pigs), domestic animals (dogs, cats), poultry, and wildlife (rabbits, pheasant, quail).

A number of methods (e.g. serotyping, short variable region [SVR] sequencing, pulsed-field gel electrophoresis [PFGE] and multilocus sequence typing [MLST]) are useful for the discrimination of C. jejuni isolates in epidemiological investigations. These methods have enabled investigators to identify the strain responsible for an outbreak. The use of MLST in particular has provided researchers with the benefit of a defined molecular fingerprint to compare strains. The recent explosion of genome sequences and comparative genomic data has increased our understanding of the epidemiology and metabolic capacity of this organism.

The identification of genetic markers predictive of ecological source and virulence potential are important to detecting and preventing the dissemination of C. jejuni via food sources. Comparative genomic studies have demonstrated that the C. jejuni population structure relates to ecological source (livestock versus non-livestock sources). Additionally, DNA sequence analysis implicates phase and allelic variation as possible mechanisms for altered gene expression and protein synthesis.

In spite of recent advances, significant gaps still exist in our knowledge of C. jejuni biology. First, researchers have yet to uncover a correlation between genomic diversity and disease severity. Second, C. jejuni virulence and disease pathology are not yet predictable on the basis of genotype. Third, the core genes necessary for disease and the variable (i.e. dispensable) genes whose products contribute to C. jejuni disease are not known. Fourth, on the basis of the observation that nucleotide changes in certain genes alter a strain’s pathogenicity, studies are needed to identify additional genes/proteins whose expression/function is influenced by nucleotide/residue variations. To address these questions, a small infectious disease animal model is needed to test the pathogenic potential of C. jejuni isolates. Continued work focusing on the relationship of genotype to phenotype is important in understanding this enigmatic organism.

Comparative studies of Campylobacter jejuni genomic diversity reveal the importance of core and dispensable genes in the biology of this enigmatic food-borne pathogen. Curr Opin Biotechnol. Apr 3 2009
MLST, DNA microarrays, and genome sequencing has allowed for a greater understanding of the metabolic capacity and epidemiology of Campylobacter jejuni. While strain-specific genes may provide an isolate a selective advantage in environments and contribute to the organism’s pathogenicity, recent work indicates that C. jejuni pathogenicity is dictated by variations in the nucleotide sequence of core genes. Challenges facing C. jejuni researchers include determining (a) the degree to which genomic diversity enables this bacterium to persist in particular environments; (b) if C. jejuni virulence and disease severity can be predicted on the basis of genotype; (c) the set of core and variable genes whose products contribute to virulence; and (d) the genes in which nucleotide changes can affect a strain’s pathogenicity.

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