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Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria

Shuoker, Bashar ; Pichler, Michael J. ; Jin, Chunsheng ; Sakanaka, Hiroka ; Wu, Haiyang ; Gascueña, Ana Martínez ; Liu, Jining ; Nielsen, Tine Sofie ; Holgersson, Jan and Nordberg Karlsson, Eva LU orcid , et al. (2023) In Nature Communications 14.
Abstract

The mucolytic human gut microbiota specialist Akkermansia muciniphila is proposed to boost mucin-secretion by the host, thereby being a key player in mucus turnover. Mucin glycan utilization requires the removal of protective caps, notably fucose and sialic acid, but the enzymatic details of this process remain largely unknown. Here, we describe the specificities of ten A. muciniphila glycoside hydrolases, which collectively remove all known sialyl and fucosyl mucin caps including those on double-sulfated epitopes. Structural analyses revealed an unprecedented fucosidase modular arrangement and explained the sialyl T-antigen specificity of a sialidase of a previously unknown family. Cell-attached sialidases and fucosidases displayed... (More)

The mucolytic human gut microbiota specialist Akkermansia muciniphila is proposed to boost mucin-secretion by the host, thereby being a key player in mucus turnover. Mucin glycan utilization requires the removal of protective caps, notably fucose and sialic acid, but the enzymatic details of this process remain largely unknown. Here, we describe the specificities of ten A. muciniphila glycoside hydrolases, which collectively remove all known sialyl and fucosyl mucin caps including those on double-sulfated epitopes. Structural analyses revealed an unprecedented fucosidase modular arrangement and explained the sialyl T-antigen specificity of a sialidase of a previously unknown family. Cell-attached sialidases and fucosidases displayed mucin-binding and their inhibition abolished growth of A. muciniphila on mucin. Remarkably, neither the sialic acid nor fucose contributed to A. muciniphila growth, but instead promoted butyrate production by co-cultured Clostridia. This study brings unprecedented mechanistic insight into the initiation of mucin O-glycan degradation by A. muciniphila and nutrient sharing between mucus-associated bacteria.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Mucins/metabolism, Neuraminidase/metabolism, alpha-L-Fucosidase/metabolism, N-Acetylneuraminic Acid/metabolism, Fucose/metabolism, Verrucomicrobia/metabolism, Polysaccharides/metabolism, Mucus/metabolism
in
Nature Communications
volume
14
article number
1833
pages
16 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:37005422
  • scopus:85151347576
ISSN
2041-1723
DOI
10.1038/s41467-023-37533-6
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
e4a88058-7020-4c4c-aceb-cdc68bc67487
date added to LUP
2023-04-18 13:20:20
date last changed
2024-06-30 05:36:06
@article{e4a88058-7020-4c4c-aceb-cdc68bc67487,
  abstract     = {{<p>The mucolytic human gut microbiota specialist Akkermansia muciniphila is proposed to boost mucin-secretion by the host, thereby being a key player in mucus turnover. Mucin glycan utilization requires the removal of protective caps, notably fucose and sialic acid, but the enzymatic details of this process remain largely unknown. Here, we describe the specificities of ten A. muciniphila glycoside hydrolases, which collectively remove all known sialyl and fucosyl mucin caps including those on double-sulfated epitopes. Structural analyses revealed an unprecedented fucosidase modular arrangement and explained the sialyl T-antigen specificity of a sialidase of a previously unknown family. Cell-attached sialidases and fucosidases displayed mucin-binding and their inhibition abolished growth of A. muciniphila on mucin. Remarkably, neither the sialic acid nor fucose contributed to A. muciniphila growth, but instead promoted butyrate production by co-cultured Clostridia. This study brings unprecedented mechanistic insight into the initiation of mucin O-glycan degradation by A. muciniphila and nutrient sharing between mucus-associated bacteria.</p>}},
  author       = {{Shuoker, Bashar and Pichler, Michael J. and Jin, Chunsheng and Sakanaka, Hiroka and Wu, Haiyang and Gascueña, Ana Martínez and Liu, Jining and Nielsen, Tine Sofie and Holgersson, Jan and Nordberg Karlsson, Eva and Juge, Nathalie and Meier, Sebastian and Morth, Jens Preben and Karlsson, Niclas G. and Abou Hachem, Maher}},
  issn         = {{2041-1723}},
  keywords     = {{Humans; Mucins/metabolism; Neuraminidase/metabolism; alpha-L-Fucosidase/metabolism; N-Acetylneuraminic Acid/metabolism; Fucose/metabolism; Verrucomicrobia/metabolism; Polysaccharides/metabolism; Mucus/metabolism}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Sialidases and fucosidases of <i>Akkermansia muciniphila</i> are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria}},
  url          = {{http://dx.doi.org/10.1038/s41467-023-37533-6}},
  doi          = {{10.1038/s41467-023-37533-6}},
  volume       = {{14}},
  year         = {{2023}},
}