Campylobacter jejuni is a species of pathogenic bacteria that is commonly associated with poultry, and is also often found in animal feces. This species of microbe is one of the most common causes of food poisoning in Europe and in the US, with the vast majority of cases occurring as isolated events rather than mass outbreaks. Active surveillance through the Foodborne Diseases Active Surveillance Network (FoodNet) indicates that about 20 cases are diagnosed each year for each 100,000 people in the US, while many more cases are undiagnosed or unreported; the CDC estimates a total of 1.5 million infections every year. The European Food Safety Authority reported 246,571 cases in 2018, and estimated approximately nine million cases of human campylobacteriosis per year in the European Union. In Africa, Asia, and the Middle East, data indicates that C. jejuni infections are endemic.

Campylobacter is a genus of bacteria that is among the most common causes of bacterial infections in humans worldwide. Campylobacter means "curved rod", deriving from the Greek kampylos (curved) and baktron (rod). Of its many species, C. jejuni is considered one of the most important from both a microbiological and public health perspective.

C. jejuni is commonly associated with poultry, and is also commonly found in animal feces. Campylobacter is a helical-shaped, non-spore-forming, Gram-negative, microaerophilic, nonfermenting motile bacterium with a single flagellum at one or both poles, which are also oxidase-positive and grow optimally at 37 to 42 °C. When exposed to atmospheric oxygen, C. jejuni is able to change into a coccal form. This species of pathogenic bacteria is one of the most common causes of human gastroenteritis in the world. Food poisoning caused by Campylobacter species can be severely debilitating, but is rarely life-threatening. It has been linked with subsequent development of Guillain–Barré syndrome, which usually develops two to three weeks after the initial illness. Individuals with recent C. jejuni infections develop Guillain-Barré syndrome at a rate of 0.3 per 1000 infections, about 100 times more often than the general population. Another chronic condition that may be associated with campylobacter infection is reactive arthritis. Reactive arthritis is a complication strongly associated with a particular genetic make-up. That is, persons who have the human leukocyte antigen B27 (HLA-B27) are most susceptible. Most often, the symptoms of reactive arthritis will occur up to several weeks after infection.

History

Campylobacter jejuni was originally named Vibrio jejuni due to its likeness to Vibrio spp. until 1963. Seabald and Vernon proposed the genus Campylobacter due to its low levels of guanine and cytosine, non-fermentative metabolism, and microaerophilic growth requirements. The first well recorded incident of Campylobacter infection occurred in 1938. Campylobacter found in milk caused diarrhea among 355 inmates in two state institutions in Illinois. The CDC, USDA and FDA collectively identified C. jejuni as responsible for over 40% of bacterial gastroenteritis found in laboratories as of 1996.

Metabolism

C. jejuni is unable to use sugars as a carbon source, primarily using amino acids for growth instead. The main reason C. jejuni lacks glycolytic capabilities is a lack of glucokinase and a lack of the 6-phosphofructokinase enzyme to employ the EMP pathway. Serine is the most important amino acid used for growth, brought into the cell by SdaC transport proteins and further broken down into pyruvate by the SdaA dehydratase. The conversion of acetyl-CoA to acetate mentioned above has substrate-level phosphorylation take place, giving another form of energy production without the use of microaerophilic respiration. Aside from these donors, C. jejuni can turn to products from the host gut microbiota including hydrogen, lactate, succinate, and formate to contribute electrons; formate, for example, is generated through intestinal mixed-acid fermentation. Infection with C. jejuni typically results in enteritis, or inflammation of the small intestine, which is characterized by abdominal pain, voluminous diarrhea (often bloody), fever, and malaise. Individuals infected with this bacteria can experience a prodromal phase of symptoms for the first 1 to 3 days, in which the more severe portion of the disease occurs. The prodromal phase presents with symptoms including rigors, high fever, body aches, and dizziness. Other than the prodromal phase, the acute diarrheal phase of enteritis usually lasts around 7 days, however abdominal pain can persist for weeks afterward. Additionally, it can also be obtained from being in contact with animals or eating undercooked seafood. C. jejuni seldomly causes disease in animals and infections are more common in lower income countries. Deadly infections are not often seen in young adults but rather among the young and elderly.

Pathogenesis

C. jejuni employs unique strategies to breach the intestinal epithelial layer of its host cells. It uses proteases, particularly HtrA, to cleverly disrupt cell junctions and temporarily traverse the cells. C. jejuni releases several different toxins, mainly enterotoxin and cytotoxins, which vary from strain to strain and correlate with the severity of the enteritis (inflammation of the small intestine). During infection, levels of all immunoglobulin classes rise. Of these, IgA is the most important because it can cross the gut wall. IgA immobilises organisms, causing them to aggregate and activate complement, and also gives short-term immunity against the infecting strain of organism. The bacteria colonize the small and large intestines, causing inflammatory diarrhea with fever. Stools contain leukocytes and blood. The role of toxins in pathogenesis is unclear. C jejuni antigens that cross-react with one or more neural structures may be responsible for triggering the Guillain–Barré syndrome.

One of the most important virulence factors of C. jejuni are flagella. The flagellar protein FlaA has been proven to be one of the abundant proteins in the cell. Flagella are required for motility, biofilm formation, host cell interactions and host colonization. The flagella in C. jejuni can also aid in the secretion intracellular proteins.

C. jejuni employs a highly sophisticated navigation system called chemotaxis. at least some of which appear to be important for competence, host adherence and invasion. C. jejuni secretes Campylobacter invasive antigens (Cia), which facilitate invasion. The bacteria also produce cytolethal distending toxins that participate in cell cycle control and induction of host cell apoptosis. C. jejuni also exploits different adaptation strategies in which the host factors seem to play a role for pathogenesis of this bacteria.

DNA repair

In the intestines, bile functions as a defensive barrier against colonization by C. jejuni. When C. jejuni is grown in a medium containing the bile acid deoxycholic acid, a component of bile, the DNA of C. jejuni is damaged by a process involving oxidative stress. which allow for successful homologous recombination. by a C. jejuni infection Moreover, surveys show that 20 to 100% of retail chickens are contaminated. This is not overly surprising, since many healthy chickens carry these bacteria in their intestinal tracts and often in high concentrations, up to 10<sup>8</sup> cfu/g. The bacteria contaminate the carcasses due to poor hygiene during the slaughter process. Several studies have shown increased concentrations of campylobacter on the carcasses after the evisceration. The impact of industrial system production systems on the chicken gut microbiome and campylobacter prevalence has also been investigated.

Raw milk is also a source of infections. The bacteria are often carried by healthy cattle and by flies on farms. Unchlorinated water may also be a source of infections. However, properly cooking chicken, pasteurizing milk, and chlorinating drinking water kill the bacteria. While Salmonella is transmitted vertically in eggs, Campylobacter is not. Therefore, consumption of eggs rarely results in human infection from campylobacter although live C. jejuni on the eggshell has been detected on retail eggs

and can contaminate the interior if it comes in contact with it, for example through the fingers or while separating the yolk from the white.

Complications

Local complications of campylobacter infections occur as a result of direct spread from the gastrointestinal tract and can include cholecystitis, pancreatitis, peritonitis, and massive gastrointestinal hemorrhage. Extraintestinal manifestations of campylobacter infection are quite rare and may include meningitis, endocarditis, septic arthritis, osteomyelitis, and neonatal sepsis. Bacteremia is detected in <1% of patients with campylobacter enteritis and is most likely to occur in patients who are immunocompromised or among the very young or very old. Transient bacteremia in immunocompetent hosts with C. jejuni enteritis may be more common but not detected because the killing action rapidly clears most normal human serotypes, and blood cultures are not routinely performed for patients with acute gastrointestinal illness.

Serious systemic illness caused by campylobacter infection rarely occurs, but can lead to sepsis and death. The case-fatality rate for campylobacter infection is 0.05 per 1000 infections. For instance, one major possible complication that C. jejuni can cause is Guillain–Barré syndrome, which induces neuromuscular paralysis in a sizeable percentage of those who suffer from it. Over time, the paralysis is typically reversible to some extent; nonetheless, about 20% of patients with GBS are left disabled, and around 5% die.

Another chronic condition that may be associated with campylobacter infection is reactive arthritis, which is strongly associated with a particular genetic make-up. That is, persons who have the human leukocyte antigen B27 (HLA-B27) are most susceptible. Most often, the symptoms of reactive arthritis will occur up to several weeks after infection. Campylobacter has a large animal reservoir, with up to 100% of poultry, including chickens, turkeys, and waterfowl, having asymptomatic intestinal infections. The major reservoirs of C. fetus are cattle and sheep. More than 90% of campylobacter infections occur during the summer months due to undercooked meats from outdoor cooking.

Europe

In 2020, there were around 120,000 cases of C. jejuni infection, which showed a decline of about 25.4% compared to the previous year. and selective culture techniques are used to distinguish it from other variants. A final diagnosis from a stool sample requires a gram stain or phase contrast microscopy.

Treatment

Campylobacter infections tend to be mild, requiring only hydration and electrolyte repletion while diarrhea lasts. Maintenance of electrolyte balance, not antibiotic treatment, is the cornerstone of treatment for campylobacter enteritis. Depending on the degree of dehydration, alternate measures may be taken including parenteral methods of hydration. Indeed, most patients with this infection have a self-limited illness and do not require antibiotics at all; however, they may be the best form of treatment in more severe cases of infection.

Antibiotic treatment

Antibiotic treatment for Campylobacter infections is usually not required nor recommended. Antibiotics are limited for treating high-risk patients including immunocompromised and older individuals. Severe cases exhibiting symptoms such as bloody stools, fever, severe abdominal pain, pregnancy, infection with HIV, and prolonged illness (symptoms that last > 1 week) may also require treatment by antibiotics which can help to shorten the duration of the symptoms. Azithromycin usage is increasing due to various drug characteristics, including its once-a-day dosage, tolerability by patients, decreased relation to Infantile hypertrophic pyloric stenosis (IHPS), and less negative symptoms; this is comparative to erythromycin. Fluoroquinolones are another source of treatment, however resistance rates of bacteria to this type of antibiotic is greatly increasing. A presence of drug-resistance to ciprofloxacin has been observed in isolate studies, as well as significant drug-resistance among campylobacter to the antibiotics nalidixic acid and tetracyclines. There is a low rate of resistance to erythromycin, the preferred source of antibiotic treatment for campylobacter infections, however resistant strains have been detected in many countries among sources of the origin of food from farm animals.

Prevention

Some simple food-handling practices can help prevent campylobacter infections. and growth under microaerophilic conditions at 42&nbsp;°C. Microaerophilic conditions are required for luxurious growth.

Suspicious colonies should be screened for oxidase and catalase activity. C. jejuni can be readily identified by commercial phenotypic assays. Alternatively, molecular assays based on PCR amplification of the 16S rRNA are also available.

Genome

The genome of C. jejuni strain NCTC11168 was published in 2000, revealing 1,641,481 base pairs (30.6% G+C) predicted to encode 1,654 proteins and 54 stable RNA species. The genome is unusual in that virtually no insertion sequences or phage-associated sequences and very few repeat sequences are found. One of the most striking findings in the genome was the presence of hypervariable sequences. These short homopolymeric runs of nucleotides were commonly found in genes encoding the biosynthesis or modification of surface structures, or in closely linked genes of unknown function. The apparently high rate of variation of these homopolymeric tracts may be important in the survival strategy of C. jejuni. The genome was re-annotated in 2007 updating 18.2% of product functions. Analysis also predicted the first pathogenicity island in C. jejuni among select strains, harbouring the bacteria's Type VI secretion system and putative cognate effectors.

Initial transposon mutagenesis screens revealed 195 essential genes, although this number is likely to go up with additional analysis.

Natural genetic transformation

C. jejuni is naturally competent for genetic transformation. Natural genetic transformation is a sexual process involving DNA transfer from one bacterium to another through the intervening medium, and the integration of the donor sequence into the recipient genome by homologous recombination. C. jejuni freely takes up foreign DNA harboring genetic information responsible for antibiotic resistance.

References

  • Campylobacter jejuni genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID
  • Current research on Campylobacter jejuni at the Norwich Research Park
  • Type strain of Campylobacter jejuni at BacDive – the Bacterial Diversity Metadatabase