Journal Article

PUBDB-2025-04191

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Uptake of fucosylated type I human milk oligosaccharide blocks by Bifidobacterium longum subsp. infantis

Ejby Hansen, M. ; Sakanaka, M. ; Jensen, M. ; Sakanaka, H. ; Pichler, M. J. ; Maeda, S. ; Franck Høvring, J. ; Nakajima, A. ; Kunstmann, S. ; Nielsen, T. S. ; Peters, G. H. J. ; Slotboom, D. J. ; Morth, J. P. ; Katayama, T. ; Abou Hachem, M. (Corresponding author)

2025
American Society for Microbiology Washington, DC

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Please use a persistent id in citations: doi:10.1128/mbio.00368-25  doi:10.3204/PUBDB-2025-04191

Abstract: Human milk oligosaccharides (HMOs) are uniquely rich in the type 1 building block disaccharide lacto-N-biose I (LNB; Galβ1,3GlcNAc), as compared to other mammals. Most HMOs are fucosylated, for example, α1,2 and α1,4 fucosylations on LNB blocks, resulting in H type 1 (H1) and Lewis a (Lea) epitopes, respectively. The dominance of Bifidobacterium in breastfed infant guts hinges on the efficient uptake of HMOs by specific ATP-binding cassette (ABC) importers. However, molecular insight into uptake of fucosylated LNB blocks is lacking. Here, we analyzed the uptake of LNB and its fucosylated H1 and Lea trisaccharides, as well as the mucin-derived disaccharide galacto-N-biose (GNB; Galβ1,3GalNAc) by an ABC importer from the HMO-utilization specialist Bifidobacterium longum subsp. infantis. Structural analyses and molecular dynamics simulations explained how fucosylated and non-fucosylated LNB forms are recognized with similar affinities by the binding protein of this importer. Strikingly, we showed that two ABC importers confer to the uptake of LNB, while the Lea trisaccharide is efficiently internalized by a single importer in B. infantis. Phylogenetic and structural analyses of bifidobacterial ABC-associated binding proteins showed that the Lea clade harbors homologs possessing internal cavities, which allows for the accommodation of branched oligosaccharides. Our work provides unique insight into the evolution and molecular basis of capture and uptake of key HMO and host-derived saccharide blocks, highlighting these compounds as hitherto unexplored candidates for fortification of infant formula.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2025

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