Campylobacter jejuni

• Describe Campylobacter jejuni- the organism

  This is a gram negative motile spiral bacteria that is microaerophilic and can grow at higher temperatures, 37-42 degrees C, in order to grow within avian species. This bacteria also belongs to the epsilon division of the proteobacteria.
• Describe the disease C. jejuni

  Classic symptoms are an acute self-limiting gastroenteritis, following an incubate period of around 2-5 days. Typically 3-10 days of inflammatory diarrhoea followed with the presence of leukocytes. Infection generally resolves without treatment but bacteremia can occur in immunocompromised. More serious cases can be treated with antibiotics, e.g., erythromycin, however resistance is problematic.
• Describe diagnosis of C. jejuni infection

  • Direct microscopy of faecal samples: spiral bacteria with characteristic rapid darting motility
  • PCR: detect the presence of hippuricase gene
  • Culture organism on antibiotic-containing selective agar plates
• Describe treatment of C. jejuni infection

  Most infected people will not seek medical support since the infection will usually resolve over a few days. Antibiotics are used in more serious cases, these are typically macrolides or fluoroquinolones, however fluoroquinolone resistance is increasingly problematic (75-90% of clinical strains are resistant).
• Describe the prevalence of campylobacter in the UK

  C. jejuni is the most common cause of bacterial gastroenteritis in the UK, and also across many high income. There is an estimated 500000 cases in England and Wales annually, with cases usually peaking around summer time. In low and middle income countries, constant exposure to C. Jejuni is thought to lead to immunity in adults, however this is associated with significant infant mortality.
• Describe the association between campylobacter and chickens

  It is estimated that 70% of campylobacter cases are linked with chicken as it is a commensal in chickens. Campylobacter colonises in very high numbers with the chicken caecum and there is not effective strategy to minimise its presence in chicken.
• Describe the difference in virulence factors of C. Jejuni compared with other bacteria

  This bacteria lacks classical virulence factors, such as T3SS, though it does have flagella based system for injecting proteins into host cells. Does not produce enterotoxins, however it possesses cytolethal distending toxin, which has an uncertain role in virulence.
• Describe the main virulence factors of C. jejuni

  • Spiral shape and flagella mediated motility
  • Ability to generate cell surface structural diversity for longer term colonisation in animal hosts
  • Mimicry of host gangliosides on cell surface by lipooligosaccharide (LOS)
  • Secretion of proteins into host cells via a flagella-based secretion system
• How does C. jejuni generate strain diversity via natural transformation?

  C. jejuni can take up DNA via a specific uptake system that allows them to transport DNA across membrane barriers and into the cytoplasm. RecA recombinase integrates the DNA into the chromosome and T2SS are essential for the uptake and transformation of DNA. Campylobacter transformation system methyltransferase methylates RAATY sites on C jejuni DNA and only methylated DNA can transform into campylobacter species.
• How does C. jejuni generate strain diversity via phase variation?

  A number of campylobacter genes contain intraegnic homopolymeric tracts, that typically consist of single nucleotide repeats of 8-12 G or C residues. These are error prone during replication so that the number of repeats varies randomly, resulting in reversible on-off switch in of production of functional protein. This influences structure of lipooligosaccharide and flagellin and creates extensive surface diversity.
• Describe lipo-oligosaccharide (LOS) in C. Jejuni

  The C. Jejuni outer membrane contains LOS in the form of a truncated structure that lacks O antigen, instead it terminates in a short oligosaccharide. This region also usually contains unusual sugar sialic acid, which resembles the sugar components of glycolipid gangliosides found on human neurones and tissues. This can potentially reduce recognition by the host, but can also result in autoimmunity due to the production of antibodies against C. Jejuni that crossreact with host cells, e.g., Guillain Barre syndrome.
• Describe the association between Guillain Barre syndrome and C. Jejuni

  Guillain-Barre syndrome is a potentially life threatening postinfectious disease characterised by rapidly progressive symmetrical weakness of the extremities. This is a result of cross reactive antibodies that attach gangliosides. Intravenous immunoglobulin and plasma exchange are effective treatments.
• Describe the capsular polysaccharide in C. jejuni

  C. jejuni strains produce an extracellular capsular polysaccharide (CPS), which can be used to stereotype strains as different strains have different repeating sugars in the CPS backbone. Lack of CPS reduces adherence to and invasion of intestinal epithelium cells and serum resistance. CPS can reduce activation of TLRs and cytokine stimulation.
• Describe protein glycosylation in C. jejuni

  C. Jejuni contains two independent systems for protein glycosylation:

  • O-linked glycosylation of flagellin: this is essential for polymerisation of flagellin to form the extracellular filament
  • N-linked glycosylation of extra cytoplasmic proteins: impacts adherence and invasion, colonisation and protection against degradation
• Describe protein secretion via the T3SS in C. jejuni

  • Flagella-based secretion system (T3SS): usually only secrets flagella proteins to construct the flagellum, but it can also secrete:
  • Cia proteins, which are involved in adherence and invasion.
  • Fed proteins, involved in establishing commensal colonisation in chickens
  • FIaC is a flagellin-like protein not required for motility but enhances invasion of human intestinal cells.