Characteristics and Pathogenic Mechanisms of the Genus Campylobacter

Characteristics of Campylobacter

Campylobacter is a genus of Gram-negative bacteria with cells that are curved or spiral-shaped, typically exhibiting an S-shape or helical form. Under old culture conditions or stress, they may also transform into coccoid forms. Campylobacter are Gram-negative bacteria. They are rapidly motile with a polar flagellum, moving in a spiral manner. They are usually microaerophilic, but some strains are facultatively anaerobic or even aerobic. They are non-spore-forming. Campylobacter species are found in many warm-blooded animals and birds, with a particular prevalence in poultry. They are also an important zoonotic pathogen.

At present, 32 formally described species and 9 subspecies are recognized, distributed in five phylogenetic groups. The most important human pathogens of this genus are C. jejuni and C. coli. C. jejuni is the most frequent bacterial cause of gastroenteritis in humans. The frequency of isolation of this organism far exceeds the more familiar intestinal pathogens E. coli, Shigella and Salmonella. C. coli, the species most closely related to C. jejuni, causes 1% to 25% of all Campylobacter diarrhea. C. coli is closely related to C. jejuni and accounts for 1% to 25% of all Campylobacter associated diarrhea cases. In addition to C. jejuni and C. coli, 13 of the other 30 species have been rarely associated with human or animal infections as pathogens. Pathogenic C. fetus, C. upsaliensis, C. insulaenigrae, and C. cryaerophila, for example, have been reported to cause bloodstream infections, periodontal infections, abscesses, meningitis, diarrhea and gastroenteritis. The lack of genomic data for most of these species has made it impossible to extensively study the patterns of intraspecies genetic variation and genome evolution in them. The question of how many of these emerging Campylobacter species cause disease and how it spreads among the hosts is still unknown.

Table 1. Currently described Campylobacter species

(Source: Fitzgerald C. 2015)

C. jejuni exhibits extensive genetic variation arising from both internal genomic mechanisms and gene exchange between different strains. Genome sequencing of C. jejuni has revealed numerous hypervariable sequences, mainly composed of homonucleotide repeats. Many of these hypervariable loci are found in genes for production or modification of the carbohydrate structures exposed on the cell surface such as capsules, lipooligosaccharides and flagella. C. jejuni is naturally competent for transformation, and thus can take up exogenous DNA from the environment. Recombination between strains has also been observed. Coupled with the frequency of transformation events, this could be responsible for the high level of genetic diversity that has been observed for this species. The frequency of natural transformation was also dependent on the concentration of carbon dioxide, as well as the bacterial cell density, which suggests that horizontal gene transfer by this mechanism may be environmentally regulated in vivo.

The lipooligosaccharides (LOS) of C. jejuni are highly diverse, which is closely related to their function in evading the immune system. Many C. jejuni LOS structures resemble neuronal gangliosides found in the human nervous system, and this molecular mimicry is considered one of the causes of autoimmune diseases. Mutations in LOS biosynthesis genes also have been shown to have an impact on the resistance of the organism to serum, and its ability to adhere and invade and human intestinal epithelial cell lines. The capsule of C. jejuni has also been shown to be important in serum resistance, epithelial cell adhesion and invasion, colonization of chickens, and virulence in a ferret model. C. jejuni strains have been serotyped for many years almost exclusively on the antigenic differences in capsule structure. So it is clear that the capsular polysaccharides are immunogenic and the extreme variability is likely an immune evasion strategy. Capsules may also be involved in protection against desiccation or bacteriophage infection, although this has not been well studied.

C. jejuni has two systems for protein glycosylation. O-linked glycosylation is the addition of glycans to serine/threonine residues of flagellar proteins, while N-linked glycosylation is the presence of glycans on asparagine residues of proteins. Since flagella and motility have a demonstrated role in C. jejuni biology, loss of motility mutations caused by O-linked glycosylation are also loss of adhesion and invasion to host cells and virulence in ferret models. N-linked glycosylation is highly conserved in all studied C. jejuni strains and C. coli, suggesting it plays a more fundamental role in C. jejuni biology.

Figure 1. The C. jejuni glycome and surface structures
(Source: Young KT, et al. 2007)

Campylobacter Symptoms

Campylobacter infection leads to several diseases such as acute enteritis, extraintestinal infections, and post-infection sequelae. Campylobacter infection is self-limiting with 5 to 7 days of symptoms and most patients do not need antibiotic treatment, with complete recovery. The relapse rate is about 5% to 10% after the first illness. Symptoms occur 2 to 5 days after the ingestion of the bacteria. They are characterized by diarrhea with abdominal cramps and acute abdominal pain. Fever, nausea, and vomiting are common. Afebrile bloody diarrhea may occur in newborns and infants.

Occasionally, healthy individuals can acquire extraintestinal infections. On the other hand, it is very much more common in immunocompromised patients, elderly patients, and pregnant women. The most common form of extraintestinal infection is bacteremia, either diarrheal or non-diarrheal. Post-infectious sequelae of Campylobacter include GBS, reactive arthritis, and irritable bowel syndrome. C. jejuni is the most common bacterial cause of GBS, and 30% of those with GBS have a preceding history of infection with C. jejuni. Reactive arthritis occurs in 2% to 5% of cases, and about a third of patients develop irritable bowel syndrome.

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