MicrobiologyBytes

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.

Related:

• Campylobacter jejuni
• Animals farmed for meat are the main source of Campylobacter infections
• How Campylobacter jejuni survives within cells
• Protein promotes antibiotic resistance in Campylobacter

Campylobacter jejuni is a curved, rod-shaped, Gram-negative bacterium commonly found in animal faeces. This genus is closely related to Helicobacter and like it has a relatively small genome (1.6-2.0 megabases) and can establish long-term associations with its hosts. Campylobacter is one of the most common causes of bacterial diarrhoea in developed countries and it is only relatively recently that we have realized the importance of this pathogen.

Many aspects of Campylobacter biology remain slightly mysterious. C. jejuni naturally colonises many bird species and is commonly associated with chickens. It is considered to be a commensal of chickens and other birds because although they commonly carry the organism, it does not cause them any disease. The reason why the organism causes disease in humans but not in chickens is not completely understood.

Contaminated food is a major source of human infections, with incorrectly prepared poultry meat the major route of infection. The organism is microaerophilic which means that it requires oxygen to survive, but that optimum growth occurs at lower levels of oxygen than are present in the atmosphere. This reflects the relatively low oxygen concentrations found in the gut.

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Infection with C. jejuni usually results in enteritis, characterised by abdominal pain, diarrhoea, fever, and sickness. The symptoms usually persist for between 24 hours and a week, but sometimes longer. The diarrhoea caused can vary in severity from loose stools to bloody diarrhoea. Although food poisoning caused by Campylobacter species can be severely debilitating, it is rarely life-threatening except in very frail patients. Antibiotics are not usually given as Campylobacter disease is usually self-limiting. However, severe or prolonged cases may require ciprofloxacin, erythromycin or norfloxacin. As with other types of diarrhoea, fluid and electrolyte replacement may be required for serious cases.

C. jejuni shows extensive genetic variation, with hypervariable sequences present in the genome. Most of these are in regions which encode proteins that are involved in the synthesis or modification of cell surface structures such as the capsule, lipooligosaccharide and flagellum. The organism is naturally competent, meaning that it can take up DNA from the environment. This allows recombination between strains, generating even more genetic diversity. Horizontal gene transfer involving both plasmid and chromosomal DNA occurs both in vitro and in vivo, and this could have an important role in rapid genome evolution and in the spread of antibiotic resistance.

The lipooligosaccharide capsule of C. jejuni is highly variable which is probably important in immune avoidance and allowing the organism to establish persistent infections. Some capsular structures resemble human neuronal gangliosides and this molecular mimicry is thought to lead to autoimmune disorders, including Guillain-Barre syndrome (GBS), a neurological complication which occurs in approximately 1 in every 1,000 cases of campylobacterosis.

C. jejuni also produces a toxin known as cytolethal distending toxin (CDT), which causes arrest at the G1/S or G2/M transition of the cell cycle, depending on the cell type. However, the role of CDT in C. jejuni pathogenesis remains unclear. At least some strains of Campylobacter can invade intestinal epithelial cells, as intracellular bacteria have been observed in patient tissues and invasion can be reproduced in cell lines in vitro.

As with many other pathogens, Toll-like receptors (TLRs) represent the first immunological challenge that C. jejuni must overcome during infection. The major adaptive immune response needed to clear C. jejuni infection primarily involves cell-mediated immunity as opposed to antibody-mediated mechanisms. This is presumably related to cellular invasion.

There is a lot we still don’t understand about the pathogenesis of C. jejuni, and our knowledge of its pathogenic mechanisms still lags considerably behind that of pathogenic bacteria such as Salmonella, Shigella, Vibrio and Listeria. Campylobacter is only distantly related to these other enteropathogens, and so has probably evolved distinct infection and virulence mechanisms which have not been observed before. More widespread understanding of the role of C. jejuni in the burden of human illness has brought this organism into the spotlight in recent years, but much work remains to be done.

Links:

• Campylobacter jejuni: molecular biology and pathogenesis. Nature Reviews Microbiology 5, 665-679 (September 2007)
• US Center for Food Safety & Applied Nutrition Online Bacteriological Analytical Manual, Chapter 7: Campylobacter
• UK Health Protection Agency: Campylobacter