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Campylobacter jejuni: molecular biology and pathogenesis

Key Points

  • Campylobacter jejuni is a major cause of foodborne bacterial illness and its prevalence rivals or even surpasses that of Salmonella foodborne infections in the developed world.

  • Both animal and environmental reservoirs can be responsible for human infection, but chickens are a primary source of sporadic human infection.

  • C. jejuni exhibits sequence diversity owing in part to hypervariable sequences in the genome as well as to efficent DNA-transformation mechanisms.

  • Despite its significance as a threat to human health, its pathogenic mechanisms have been poorly explored compared with those of other bacterial pathogens. Progress-limiting issues have been the lack of tractable genetic tools as well as inconvenient or poor animal models of disease.

  • Genomic and genetic analyses of C. jejuni have revealed mechanisms of pathogenicity and chick colonization. Pathogenicity is multi-factorial and requires the presence of the flagella, the capsule, both O-linked and N-linked protein glycosylation and secreted proteins that facilitate host-cell invasion.

  • C. jejuni is a pathogen in humans, but a commensal species in chickens. The immune responses and/or bacterial colonization features might therefore be host specific.

Abstract

Campylobacter jejuni is a foodborne bacterial pathogen that is common in the developed world. However, we know less about its biology and pathogenicity than we do about other less prevalent pathogens. Interest in C. jejuni has increased in recent years as a result of the growing appreciation of its importance as a pathogen and the availability of new model systems and genetic and genomic technologies. C. jejuni establishes persistent, benign infections in chickens and is rapidly cleared by many strains of laboratory mouse, but causes significant inflammation and enteritis in humans. Comparing the different host responses to C. jejuni colonization should increase our understanding of this organism.

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Figure 1: The sources and outcomes of Campylobacter jejuni infection.
Figure 2: The Campylobacter jejuni glycome and surface structures.
Figure 3: O- and N-linked glycosylation in Campylobacter jejuni.
Figure 4: Uptake and activity of cytolethal distending toxin.
Figure 5: Molecular and cellular features of the innate immune response to Campylobacter jejuni in humans and chickens.

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Acknowledgements

Research on Campylobacter in the authors' laboratory is supported by the USDA Food Safety Programme. K.T.Y. is a predoctoral fellow of the Howard Hughes Medical Institute, Maryland, USA. L.M.D. is supported by the Genetics Training Program at the University of Michigan, Michigan, USA.

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DATABASES

Entrez Genome

pVir

RM1221

11168

81-176

Entrez Genome Project

Actinobacillus actinomycetemcomitans

Bacillus subtilis

Campylobacter coli

Campylobacter jejuni

Escherichia coli

Haemophilus ducreyi

Helicobacter hepaticus

Helicobacter pylori

Neisseria gonorrhoeae

Vibrio cholerae

Wolinella succinogenes

Entrez Protein

CadF

CetA

CetB

CbrR

CdtA

CdtB

CdtC

CDT

CheV

CheY

CiaB

Cj1496c

FlaC

JlpA

NOD1

Peb1

TLR-5

TLR-9

σ28

σ54

Entrez Gene

Cj1496c

Glossary

Signature-tagged mutagenesis

A method for simultaneously screening pools of bacteria that have transposon-generated mutations that is used to identify genes that are required for survival under the conditions specified by the investigator. Widely used to identify genes in bacterial pathogens that are required for virulence or colonization.

Type IV secretion system

A bacterial secretion system that is related to bacterial conjugative pili and that consists of a secretion channel and often a pilus structure. It is involved in the secretion of proteins and/or DNA between two bacterial cells or between a bacterial cell and a eukaryotic cell.

Homopolymeric tract

A stretch of DNA that contains multiple repetitions of a single nucleotide. It can lead to slipped-strand mispairing, which can result in variation in the length of the homopolymeric tract and, potentially, phase variation.

Lipooligosaccharide

(LOS). Found in the outer leaflet of the outer membrane of some Gram-negative bacteria. LOS consists of lipid A linked to a polysaccharide, but lacks the Ospecific polysaccharide of the LOS that is found in other Gram-negative bacteria.

Phase variation

A heritable but reversible 'on and off' switch that regulates the expression of a gene or operon.

Type II secretion system

A bacterial secretion system that transports proteins across the outer membrane after they have been transported across the inner membrane by the Sec or Tat machinery.

Two-component system

Comprises two proteins, a sensor and a response regulator, that act together to regulate a cellular process (or processes). The sensor contains a histidine kinase domain that regulates the level of phosphorylation and, consequently, the activity of the response regulator (which is often, but not always, DNA binding and transcriptional regulation).

Type III secretion system

A bacterial secretion system that consists of a needle-like apparatus that transports proteins from the bacterial cytoplasm directly into the cytoplasm of a eukaryotic cell.

ATP-binding cassette (ABC) transporter

A member of a large family of proteins that uses the energy provided by the hydrolysis of ATP to transport substrates across membranes.

T helper (TH)-1 versus TH-2

A T helper (TH) cell is derived from one of two subsets that regulate the immune response through the secretion of cytokines. TH-1 mediates an inflammatory, cell-mediated response, whereas TH-2 cell activity enhances the humoral response and suppresses cell-mediated responses.

Toll-like receptor

(TLR). A key recognition molecule in the host innate immune response. A membrane-spanning protein that recognizes conserved ligands on pathogens, such as flagellin, lipopolysaccharide or DNA. Such ligands are widely found in pathogens and are known as pathogen-associated molecular patterns.

Cyclic-di-GMP regulation

Regulation through the second-messenger cyclic-di-GMP. This molecule is generated by diguanylate cyclases, which often carry the conserved residues GGDEF, and is hydrolysed by phosphodiesterase A, which often carries the conserved residues EAL. These regulatory domains are found in a wide range of proteins, thereby allowing various input signals to influence the production or hydrolysis of the second messenger.

Heterophil

A granular leukocyte that is defined by its variable size and staining characteristics; the human version is the neutrophil.

Complement-mediated killing

The binding of an antibody to an antigen often triggers the complement system, which comprises approximately 30 proteins. A proteolytic cascade sequentially activates the complement proteins, which results in the formation of a complex and either opsonization or lysis of the foreign material.

Humoral response

The humoral immune response refers to the production of antibodies for pathogen clearance. The term encompasses complement activation, opsonization, TH2 activation and cytokine production.

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Young, K., Davis, L. & DiRita, V. Campylobacter jejuni: molecular biology and pathogenesis. Nat Rev Microbiol 5, 665–679 (2007). https://doi.org/10.1038/nrmicro1718

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