Gut microbiome ADP-ribosyltransferases are widespread phage-encoded fitness factors.
ADP Ribose Transferases
/ genetics
Actin Cytoskeleton
/ metabolism
Animals
Bacteriophages
/ genetics
Bacteroides
/ metabolism
Bacteroides thetaiotaomicron
/ metabolism
Caco-2 Cells
Cell Line, Tumor
Epithelial Cells
/ metabolism
Feces
/ chemistry
Female
Gastrointestinal Microbiome
/ genetics
Germ-Free Life
HT29 Cells
Humans
Inosine
/ metabolism
Intestinal Mucosa
/ metabolism
Male
Mice
Mice, Inbred C57BL
Myosin Heavy Chains
/ metabolism
ADP-ribosylation
ADP-ribosyltransferases
Bacteriophages
Bacteroides
Microbiome
biofilms
cytoskeleton
fitness factor
gut colonization
inosine
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
08 09 2021
08 09 2021
Historique:
received:
21
10
2020
revised:
23
06
2021
accepted:
22
07
2021
pubmed:
18
8
2021
medline:
14
1
2022
entrez:
17
8
2021
Statut:
ppublish
Résumé
Bacterial ADP-ribosyltransferases (ADPRTs) have been described as toxins involved in pathogenesis through the modification of host proteins. Here, we report that ADPRTs are not pathogen restricted but widely prevalent in the human gut microbiome and often associated with phage elements. We validated their biochemical activity in a large clinical isolate collection and further examined Bxa, a highly abundant ADPRT in Bacteroides. Bxa is expressed, secreted, and enzymatically active in Bacteroides and can ADP-ribosylate non-muscle myosin II proteins. Addition of Bxa to epithelial cells remodeled the actin cytoskeleton and induced secretion of inosine. Bxa-encoding B. stercoris can use inosine as a carbon source and colonizes the gut to significantly greater numbers than a bxa-deleted strain in germ-free and altered Schaedler flora (ASF) mice. Colonization correlated with increased inosine concentrations in the feces and tissues. Altogether, our results show that ADPRTs are abundant in the microbiome and act as bacterial fitness factors.
Identifiants
pubmed: 34403684
pii: S1931-3128(21)00344-9
doi: 10.1016/j.chom.2021.07.011
pmc: PMC8429246
mid: NIHMS1733866
pii:
doi:
Substances chimiques
Inosine
5A614L51CT
ADP Ribose Transferases
EC 2.4.2.-
Myosin Heavy Chains
EC 3.6.4.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1351-1365.e11Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK043351
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK097485
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109725
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142784
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests R.J.X. is a consultant to Novartis.
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