ArticleJournal of applied microbiology2018
Overexpression of O-polysaccharide chain length regulators in Gram-negative bacteria using the Wzx-/Wzy-dependent pathway enhances production of defined modal length O-polysaccharide polymers for use as haptens in glycoconjugate vaccines.
Article in Journal of applied microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Genetic engineering ofEcoSal Plus · 2024Review
- Repeat-Unit Elongations To Produce Bacterial Complex Long Polysaccharide Chains, an O-Antigen Perspective.EcoSal Plus · 2023Review
- Evaluation of Three Candidate Live-AttenuatedVaccines · 2023Article
- The effect of O-antigen length determinant wzz on the immunogenicity of Salmonella Typhimurium for Escherichia coli O2 O-polysaccharides delivery.Veterinary research · 2023Article
- Reduced immunogenicity of a liveFrontiers in immunology · 2023Article
- Impact and Control of Sugar Size in Glycoconjugate Vaccines.Molecules (Basel, Switzerland) · 2022Review
- Combined effects of glycan chain length and linkage type on the immunogenicity of glycoconjugate vaccines.NPJ vaccines · 2021Review
- Advances in the development of Salmonella-based vaccine strategies for protection against Salmonellosis in humans.Journal of applied microbiology · 2021Review
- Effect of O-Antigen Chain Length Regulation on the Immunogenicity ofInternational journal of molecular sciences · 2021Article
- Synthesis and delivery ofProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Identification of the Pseudomonas aeruginosa O17 and O15 O-Specific Antigen Biosynthesis Loci Reveals an ABC Transporter-Dependent Synthesis Pathway and Mechanisms of Genetic Diversity.Journal of bacteriology · 2020Article
- Unique Regions of the Polysaccharide Copolymerase WzzJournal of bacteriology · 2019Article
- Glycoconjugate vaccine using a genetically modified O antigen induces protective antibodies toProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Classical and novel strategies to develop aHuman vaccines & immunotherapeutics · 2019Review
- Maternal Antibodies Elicited by Immunization With an O- Polysaccharide Glycoconjugate Vaccine Protect Infant Mice Against LethalFrontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
aimsO-polysaccharide (OPS) molecules are protective antigens for several bacterial pathogens, and have broad utility as components of glycoconjugate vaccines. Variability in the OPS chain length is one obstacle towards further development of these vaccines. Introduction of sizing steps during purification of OPS molecules of suboptimal or of mixed lengths introduces additional costs and complexity while decreasing the final yield. The overall goal of this study was to demonstrate the utility of engineering Gram-negative bacteria to produce homogenous O-polysaccharide populations that can be used as the basis of carbohydrate vaccines by overexpressing O-polysaccharide chain length regulators of the Wzx-/Wzy-dependent pathway. METHOD AND
resultsThe O-polysaccharide chain length regulators wzzB and fepE from Salmonella Typhimurium I77 and wzz2 from Pseudomonas aeruginosa PAO1 were cloned and expressed in the homologous organism or in other Gram-negative bacteria. Overexpression of these Wzz proteins in the homologous organism significantly increased the proportion of long or very long chain O-polysaccharides. The same observation was made when wzzB was overexpressed in Salmonella Paratyphi A and Shigella flexneri, and wzz2 was overexpressed in two other strains of P. aeruginosa.
conclusionsOverexpression of Wzz proteins in Gram-negative bacteria using the Wzx/Wzy-dependant pathway for lipopolysaccharide synthesis provides a genetic method to increase the production of an O-polysaccharide population of a defined size. SIGNIFICANCE AND IMPACT OF THE STUDY: The methods presented herein represent a cost-effective and improved strategy for isolating preferred OPS vaccine haptens, and could facilitate the further use of O-polysaccharides in glycoconjugate vaccine development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.