A multi-enzyme machine polymerizes the Haemophilus influenzae type b capsule.
Nat Chem Biol
; 19(7): 865-877, 2023 07.
Article
in En
| MEDLINE
| ID: mdl-37277468
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Haemophilus Vaccines
/
Haemophilus influenzae type b
/
Haemophilus Infections
Limits:
Child
/
Humans
/
Infant
Language:
En
Journal:
Nat Chem Biol
Journal subject:
BIOLOGIA
/
QUIMICA
Year:
2023
Document type:
Article
Affiliation country:
Spain