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. C. jejuni was first discovered in the small intestines of humans in the 1970s, however, symptoms have been noted since the early 20th century. 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 . The four main amino acids C. jejuni takes in are serine, aspartate, asparagine, and glutamate, which are listed in order of preference. If all of these are depleted, some strains can use proline as well. Either the host or metabolic activity of other gut microbes can supply these amino acids.
The metabolic pathways C. jejuni is capable of include the , a non-oxidative pentose phosphate pathway, gluconeogenesis, and fatty acid synthesis. 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. Though this pyruvate cannot directly be converted into phosphoenolpyruvic acid (as C. jejuni lacks this synthetase), the pyruvate can enter the TCA cycle to form oxaloacetic acid intermediates that can be converted to phosphoenolpyruvic acid for gluconeogenesis. This production of carbohydrates is important for the virulence factors of C. jejuni. The pyruvate created from serine can also be converted to acetyl CoA and be applied to fatty acid synthesis or continue into the TCA cycle to create precursors for other biosynthetic pathways. Aspartate and glutamate are both brought into the cell via Peb1A transport proteins. Glutamate can be transaminated into aspartate, and aspartate can be deaminated to make fumerate that feeds into the TCA cycle as well. Asparagine is also able to be deaminated into aspartate (which follows the process into the TCA cycle mentioned above). While the amino acids listed above are able to be metabolized, C. jejuni is capable of taking in many of the other amino acids which helps to lower the anabolic cost of de novo synthesis.
If other sources of carbon are exhausted, C. jejuni can also use acetate and lactate as carbon sources. Acetate is a normal secreted byproduct of C. jejuni metabolism stemming from the recycling of CoA, and the absence of other carbon sources can cause C. jejuni to "switch" this reaction to take in acetate for the conversion to acetyl-CoA (catalyzed by phosphate acetyltransferase and acetate kinase enzymes). Lactate is a normal byproduct of many fermentative bacteria in the gut, and C. jejuni can take in and oxidize this lactate to supply pyruvate through the activity of dehydrogenase iron-sulfur enzyme complexes.
The energetic needs of these anabolic pathways are met in multiple ways. The cytochrome c and quinol terminal oxidases allow for C. jejuni to use oxygen as a terminal electron acceptor for the reduced carriers produced through the TCA cycle (hence why C. jejuni is considered an obligate microaerophile). 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.
C. jejuni can use many different electron donors for its metabolic processes, using NADH and FADH most commonly – though C. jejuni uses NADH poorly compared to FADH due to a replacement of genes encoding subunits for NADH dehydrogenases for genes contributing to processes relating to FADH electron donation. 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. Unlike almost all other Campylobacter or Helicobacter species, C. jejuni can also accept electrons from sulfite and metabisulfite through its cytochrome c oxidoreductase system.
While oxygen is mainly used as a terminal electron acceptor, C. jejuni can use nitrate, nitrite, sulfur oxides (such as dimethyl sulfoxide or trimethylamine N-oxide), or fumarate as terminal electron acceptors as well to survive as a microaerophilic bacterium. Due to oxygen-limited conditions in the common areas of colonization, C. jejuni possesses two separate terminal oxidases with different affinities for oxygen, where the low affinity oxidase can directly retrieve electrons from menaquinones. The adaptations allowing for multiple electron acceptors help to combat the problem with reactive oxygen species arising from the sole use of oxygen as well; C. jejuni cannot grow under strictly aerobic conditions. Enzymes C. jejuni carries to impede the effects of reactive oxygen species include: superoxide dismutase SodB, alkyl hydroxide reductase AhpC, catalase KatA, and thiol peroxidases Tpx and Bcp.
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. Antibiotic resistance genes are more frequently transferred in biofilms than between planktonic cells (single cells that float in liquid media).
Sources Campylobacter jejuni is commonly associated with poultry, and it naturally colonises the digestive tract of many bird species. All types of poultry and wild birds can become colonized with campylobacter. One study found that 30% of European starlings in farm settings in Oxfordshire, United Kingdom, were carriers of C. jejuni. It is also common in cattle, and although it is normally a harmless commensal of the gastrointestinal tract in these animals, it can cause campylobacteriosis in calves. It has also been isolated from wombat and kangaroo feces, being a cause of bushwalkers' diarrhea. Contaminated drinking water and unpasteurized milk provide an efficient means for distribution. Contaminated food is a major source of isolated infections, with incorrectly prepared meat and poultry as the primary source of the bacteria. 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 108 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. Studies have investigated the chicken microbiome to understand how, why and when campylobacter appears within the chicken gut. 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.
Transmission