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Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
- Source :
-
BMC veterinary research [BMC Vet Res] 2019 Jan 03; Vol. 15 (1), pp. 6. Date of Electronic Publication: 2019 Jan 03. - Publication Year :
- 2019
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Abstract
- Background: Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry. Virulence can largely be attributed to the secretion of a series of haemolytic toxins, which are highly immunogenic. A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues. Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt. Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T). However to date, there is little evidence to suggest that such a glucose polymer is formed on its target peptides in A. pleuropneumoniae. Both the toxins and glycosylation system represent potential targets for the basis of a vaccine against A. pleuropneumoniae infection.<br />Results: In this study, we developed cytoplasmic glycoengineering to construct glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose. We transferred ngt and agt to the chromosome of Escherichia coli in order to generate a native-like operon for glycoengineering. A single chromosomal copy of ngt and agt resulted in the glucosylation of toxin fragments by a short glycan, rather than a polymer.<br />Conclusions: A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
- Subjects :
- Actinobacillus Infections immunology
Actinobacillus Infections prevention & control
Animals
Escherichia coli genetics
Genetic Engineering methods
Genetic Engineering veterinary
Glycoconjugates genetics
Glycoconjugates immunology
Microorganisms, Genetically-Modified genetics
Pleuropneumonia immunology
Pleuropneumonia prevention & control
Pleuropneumonia veterinary
Swine
Swine Diseases immunology
Swine Diseases microbiology
Swine Diseases prevention & control
Vaccines, Conjugate immunology
Actinobacillus Infections veterinary
Actinobacillus pleuropneumoniae immunology
Bacterial Toxins immunology
Bacterial Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1746-6148
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC veterinary research
- Publication Type :
- Academic Journal
- Accession number :
- 30606265
- Full Text :
- https://doi.org/10.1186/s12917-018-1751-2