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Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides

Pasteurella multocida, an encapsulated gram-negative bacterium, is a significant veterinary pathogen. The P. multocida is classified into 5 serogroups (A, B, D, E, and F) based on the bacterial capsular polysaccharide (CPS), which is important for virulence. Serogroups B and E are the primary causat...

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Autores principales: Richardson, Nicole I, Ravenscroft, Neil, Kuttel, Michelle M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627249/
https://www.ncbi.nlm.nih.gov/pubmed/37334939
http://dx.doi.org/10.1093/glycob/cwad049
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author Richardson, Nicole I
Ravenscroft, Neil
Kuttel, Michelle M
author_facet Richardson, Nicole I
Ravenscroft, Neil
Kuttel, Michelle M
author_sort Richardson, Nicole I
collection PubMed
description Pasteurella multocida, an encapsulated gram-negative bacterium, is a significant veterinary pathogen. The P. multocida is classified into 5 serogroups (A, B, D, E, and F) based on the bacterial capsular polysaccharide (CPS), which is important for virulence. Serogroups B and E are the primary causative agents of bovine hemorrhagic septicemia that is associated with significant yearly losses of livestock worldwide, primarily in low- and middle-income countries. The P. multocida disease is currently managed by whole-cell vaccination, albeit with limited efficacy. CPS is an attractive antigen target for an improved vaccine: CPS-based vaccines have proven highly effective against human bacterial diseases and could provide longer-term protection against P. multocida. The recently elucidated CPS repeat units of serogroups B and E both comprise a N-acetyl-β-D-mannosaminuronic acid/N-acetyl-β-D-glucosamine disaccharide backbone with β-D-fructofuranose (Fruf) side chain, but differ in their glycosidic linkages, and a glycine (Gly) side chain in serogroup B. Interestingly, the Haemophilus influenzae types e and d CPS have the same backbone residues. Here, comparative modeling of P. multocida serogroups B and E and H. influenzae types e and d CPS identifies a significant impact of small structural differences on both the chain conformation and the exposed potential antibody-binding epitopes (Ep). Further, Fruf and/or Gly side chains shield the immunogenic amino-sugar CPS backbone—a possible common strategy for immune evasion in both P. multocida and H. influenzae. As the lack of common epitopes suggests limited potential for cross-reactivity, a bivalent CPS-based vaccine may be necessary to provide adequate protection against P. multocida types B and E.
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spelling pubmed-106272492023-11-07 Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides Richardson, Nicole I Ravenscroft, Neil Kuttel, Michelle M Glycobiology Original Article Pasteurella multocida, an encapsulated gram-negative bacterium, is a significant veterinary pathogen. The P. multocida is classified into 5 serogroups (A, B, D, E, and F) based on the bacterial capsular polysaccharide (CPS), which is important for virulence. Serogroups B and E are the primary causative agents of bovine hemorrhagic septicemia that is associated with significant yearly losses of livestock worldwide, primarily in low- and middle-income countries. The P. multocida disease is currently managed by whole-cell vaccination, albeit with limited efficacy. CPS is an attractive antigen target for an improved vaccine: CPS-based vaccines have proven highly effective against human bacterial diseases and could provide longer-term protection against P. multocida. The recently elucidated CPS repeat units of serogroups B and E both comprise a N-acetyl-β-D-mannosaminuronic acid/N-acetyl-β-D-glucosamine disaccharide backbone with β-D-fructofuranose (Fruf) side chain, but differ in their glycosidic linkages, and a glycine (Gly) side chain in serogroup B. Interestingly, the Haemophilus influenzae types e and d CPS have the same backbone residues. Here, comparative modeling of P. multocida serogroups B and E and H. influenzae types e and d CPS identifies a significant impact of small structural differences on both the chain conformation and the exposed potential antibody-binding epitopes (Ep). Further, Fruf and/or Gly side chains shield the immunogenic amino-sugar CPS backbone—a possible common strategy for immune evasion in both P. multocida and H. influenzae. As the lack of common epitopes suggests limited potential for cross-reactivity, a bivalent CPS-based vaccine may be necessary to provide adequate protection against P. multocida types B and E. Oxford University Press 2023-06-19 /pmc/articles/PMC10627249/ /pubmed/37334939 http://dx.doi.org/10.1093/glycob/cwad049 Text en © The Author(s) 2023. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Richardson, Nicole I
Ravenscroft, Neil
Kuttel, Michelle M
Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides
title Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides
title_full Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides
title_fullStr Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides
title_full_unstemmed Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides
title_short Conformational comparisons of Pasteurella multocida types B and E and structurally related capsular polysaccharides
title_sort conformational comparisons of pasteurella multocida types b and e and structurally related capsular polysaccharides
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627249/
https://www.ncbi.nlm.nih.gov/pubmed/37334939
http://dx.doi.org/10.1093/glycob/cwad049
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