title: A bacterial homolog of a eukaryotic inositol phosphate signaling enzyme mediates cross-kingdom dialog in the mammalian gut.
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 Ca(2+) signaling. Our characterization of BtMinpp offers several directions for understanding how the microbiome serves human gastrointestinal physiology.
authors: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK.
authors: Régis
authors: R
authors: Stentz
authors: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK.
authors: Samantha
authors: S
authors: Osborne
authors: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK.
authors: Nikki
authors: N
authors: Horn
authors: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
authors: Arthur W H
authors: AW
authors: Li
authors: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK.
authors: Isabelle
authors: I
authors: Hautefort
authors: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK.
authors: Roy
authors: R
authors: Bongaerts
authors: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK.
authors: Marine
authors: M
authors: Rouyer
authors: Department of Computational and Systems Biology, John Innes Centre, Norwich NR4 7UH, UK.
authors: Paul
authors: P
authors: Bailey
authors: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors: Stephen B
authors: SB
authors: Shears
authors: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK; School of Chemistry, University of East Anglia, Norwich NR4 7TJ, UK.
authors: Andrew M
authors: AM
authors: Hemmings
authors: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK. Electronic address: c.brearley@uea.ac.uk.
authors: Charles A
authors: CA
authors: Brearley
authors: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UK; Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK. Electronic address: simon.carding@ifr.ac.uk.
authors: Simon R
authors: SR
authors: Carding
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001439:Bacteroides / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D020013:Calcium Signaling; D020134:Catalytic Domain; D019073:HT29 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D008969:Molecular Sequence Data; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D059748:Proteolysis
chemical_list: D001426:Bacterial Proteins; D010744:Phosphoric Monoester Hydrolases; C064119:multiple inositol-polyphosphate phosphatase