Gut microbiome ADP-ribosyltransferases are widespread phage-encoded fitness factors.
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Abstract | 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. |
Year of Publication | 2021
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Journal | Cell Host Microbe
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Volume | 29
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Issue | 9
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Pages | 1351-1365.e11
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Date Published | 2021 09 08
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ISSN | 1934-6069
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DOI | 10.1016/j.chom.2021.07.011
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PubMed ID | 34403684
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PubMed Central ID | PMC8429246
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Grant list | P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 DK097485 / DK / NIDDK NIH HHS / United States
U19 AI109725 / AI / NIAID NIH HHS / United States
U19 AI142784 / AI / NIAID NIH HHS / United States
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