A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut

Stentz, Régis, Osborne, Samantha, Horn, Nikki, Li, Arthur, Hautefort, Isabelle, Bongaerts, Roy, Rouyer, Marine, Bailey, Paul, Shears, Stephen B., Hemmings, Andrew, Brearley, Charles A. and Carding, Simon (2014) A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut. Cell Reports, 6 (4). pp. 646-656. ISSN 2211-1247

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Abstract

Dietary InsP6 can modulate eukaryotic cell proliferation and has complex nutritive consequences, but its metabolism in the mammalian gastrointestinal tract is poorly understood. Therefore, we performed phylogenetic analyses of the gastrointestinal microbiome in order to search for candidate InsP6 phosphatases. We determined that prominent gut bacteria express homologs of the mammalian InsP6 phosphatase (MINPP) and characterized the enzyme from Bacteroides thetaiotaomicron (BtMinpp). We show that BtMinpp has exceptionally high catalytic activity, which we rationalize on the basis of mutagenesis studies and by determining its crystal structure at 1.9 Å resolution. We demonstrate that BtMinpp is packaged inside outer membrane vesicles (OMVs) protecting the enzyme from degradation by gastrointestinal proteases. Moreover, we uncover an example of cross-kingdom cell-to-cell signaling, showing that the BtMinpp-OMVs interact with intestinal epithelial cells to promote intracellular Ca2+ signaling. Our characterization of BtMinpp offers several directions for understanding how the microbiome serves human gastrointestinal physiology.

Item Type: Article
Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Faculty \ School: Faculty of Science
Faculty of Science > School of Biological Sciences
Faculty of Science > School of Chemistry
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 26 Mar 2014 13:10
Last Modified: 17 Sep 2020 23:55
URI: https://ueaeprints.uea.ac.uk/id/eprint/48285
DOI: 10.1016/j.celrep.2014.01.021

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