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

Area of Science:

• Veterinary Microbiology
• Immunology
• Structural Biology

Background:

• Pasteurella multocida is a major veterinary pathogen causing significant livestock losses globally.
• Current whole-cell vaccines for P. multocida offer limited efficacy.
• Capsular polysaccharides (CPS) are key virulence factors and promising vaccine targets.

Purpose of the Study:

• To investigate the structural basis of P. multocida serogroups B and E capsular polysaccharides (CPS).
• To compare P. multocida CPS with Haemophilus influenzae CPS to understand immune evasion strategies.
• To inform the development of improved, potentially bivalent, CPS-based vaccines.

Main Methods:

• Elucidation of CPS repeat unit structures for P. multocida serogroups B and E.
• Comparative molecular modeling of P. multocida (serogroups B, E) and H. influenzae (types e, d) CPS.
• Analysis of structural differences and their impact on potential antibody-binding epitopes.

Main Results:

• P. multocida serogroups B and E share a common CPS backbone but differ in glycosidic linkages and side chains (fructofuranose and glycine).
• Structural variations significantly alter CPS chain conformation and exposed antibody-binding epitopes.
• Fructofuranose and glycine side chains may shield the immunogenic CPS backbone, facilitating immune evasion.

Conclusions:

• Small structural differences in CPS significantly impact antigenicity and immune recognition.
• The identified structural variations suggest limited cross-reactivity between serogroups B and E.
• A bivalent CPS-based vaccine targeting both P. multocida serogroups B and E is likely required for broad protection.