TY - JOUR
AU1 - Litschko, Christa
AU2 - Di Domenico, Valerio
AU3 - Schulze, Julia
AU4 - Li, Sizhe
AU5 - Ovchinnikova, Olga G.
AU6 - Voskuilen, Thijs
AU7 - Bethe, Andrea
AU8 - Cifuente, Javier O.
AU9 - Marina, Alberto
AU1 - Budde, Insa
AU1 - Mast, Tim A.
AU1 - Sulewska, Małgorzata
AU1 - Berger, Monika
AU1 - Buettner, Falk F. R.
AU1 - Lowary, Todd L.
AU1 - Whitfield, Chris
AU1 - Codée, Jeroen D. C.
AU1 - Schubert, Mario
AU1 - Guerin, Marcelo E.
AU2 - Fiebig, Timm
AB - Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes are potential drug targets and valuable biotechnological tools for generating vaccine antigens. Despite their importance, it remains unknown how structurally variable capsule polymers of Gram-negative pathogens are linked to the conserved glycolipid anchoring these virulence factors to the bacterial membrane. Using Actinobacillus pleuropneumoniae as an example, we demonstrate that CpsA and CpsC generate a poly(glycerol-3-phosphate) linker to connect the glycolipid with capsules containing poly(galactosylglycerol-phosphate) backbones. We reconstruct the entire capsule biosynthesis pathway in A. pleuropneumoniae serotypes 3 and 7, solve the X-ray crystal structure of the capsule polymerase CpsD, identify its tetratricopeptide repeat domain as essential for elongating poly(glycerol-3-phosphate) and show that CpsA and CpsC stimulate CpsD to produce longer polymers. We identify the CpsA and CpsC product as a wall teichoic acid homolog, demonstrating similarity between the biosynthesis of Gram-positive wall teichoic acid and Gram-negative capsules.[graphic not available: see fulltext]
TI - Transition transferases prime bacterial capsule polymerization
JF - Nature Chemical Biology
DO - 10.1038/s41589-024-01664-8
DA - 2025-01-01
UR - https://www.deepdyve.com/lp/springer-journals/transition-transferases-prime-bacterial-capsule-polymerization-yuQPtRuFEf
SP - 120
EP - 130
VL - 21
IS - 1
DP - DeepDyve
ER -