Campylobacter jejuni

Campylobacter jejuniCampylobacter 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.

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