A multi-enzyme machine polymerizes the Haemophilus influenzae type b capsule

Bacterial capsules have critical roles in host-pathogen interactions. They provide a protective envelope against host recognition, leading to immune evasion and bacterial survival. Here we define the capsule biosynthesis pathway of Haemophilus influenzae serotype b (Hib), a Gram-negative bacterium t...

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Detalhes bibliográficos
Autores: Cifuente, Javier O., Schulze, Julia, Bethe, Andrea, Domenico, Valerio Di, Litschko, Christa, Budde, Insa, Eidenberger,Lukas, Thiesler, Hauke, Ramón Roth,Isabel, Berger, Monika, Claus, Heike, D’Angelo, Cecilia, Marina, A., Gerardy-Schahn, Rita, Schubert, Mario, Guerin, Marcelo E., Fiebig, Timm
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/377743
Acesso em linha:http://hdl.handle.net/10261/377743
Access Level:acceso abierto
Palavra-chave:Carbohydrates
Enzyme mechanisms
Glycobiology
Vaccines
X-ray crystallography
Descrição
Resumo:Bacterial capsules have critical roles in host-pathogen interactions. They provide a protective envelope against host recognition, leading to immune evasion and bacterial survival. Here we define the capsule biosynthesis pathway of Haemophilus influenzae serotype b (Hib), a Gram-negative bacterium that causes severe infections in infants and children. Reconstitution of this pathway enabled the fermentation-free production of Hib vaccine antigens starting from widely available precursors and detailed characterization of the enzymatic machinery. The X-ray crystal structure of the capsule polymerase Bcs3 reveals a multi-enzyme machine adopting a basket-like shape that creates a protected environment for the synthesis of the complex Hib polymer. This architecture is commonly exploited for surface glycan synthesis by both Gram-negative and Gram-positive pathogens. Supported by biochemical studies and comprehensive 2D nuclear magnetic resonance, our data explain how the ribofuranosyltransferase CriT, the phosphatase CrpP, the ribitol-phosphate transferase CroT and a polymer-binding domain function as a unique multi-enzyme assembly.

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