HupA, the main undecaprenyl pyrophosphate and phosphatidylglycerol phosphate phosphatase in Helicobacter pylori is essential for colonization of the stomach.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, c2005-
    • Subject Terms:
      Bacterial Outer Membrane Proteins/*metabolism ; Helicobacter pylori/*metabolism; Amino Acid Sequence ; Animals ; Bacterial Outer Membrane Proteins/physiology ; Carrier Proteins/metabolism ; Cell Membrane/metabolism ; Cell Wall/metabolism ; DNA-Binding Proteins ; Escherichia coli/metabolism ; Escherichia coli Proteins/metabolism ; Female ; Helicobacter pylori/pathogenicity ; Mice ; Mice, Inbred Strains ; Microbial Sensitivity Tests ; Phosphatidate Phosphatase ; Phosphoric Monoester Hydrolases/metabolism ; Polyisoprenyl Phosphates/metabolism ; Polymyxin B/pharmacology ; Pyrophosphatases/metabolism ; Stomach
    • Abstract:
      The biogenesis of bacterial cell-envelope polysaccharides requires the translocation, across the plasma membrane, of sugar sub-units that are produced inside the cytoplasm. To this end, the hydrophilic sugars are anchored to a lipid phosphate carrier (undecaprenyl phosphate (C55-P)), yielding membrane intermediates which are translocated to the outer face of the membrane. Finally, the glycan moiety is transferred to a nascent acceptor polymer, releasing the carrier in the "inactive" undecaprenyl pyrophosphate (C55-PP) form. Thus, C55-P is generated through the dephosphorylation of C55-PP, itself arising from either de novo synthesis or recycling. Two types of integral membrane C55-PP phosphatases were described: BacA enzymes and a sub-group of PAP2 enzymes (type 2 phosphatidic acid phosphatases). The human pathogen Helicobacter pylori does not contain BacA homologue but has four membrane PAP2 proteins: LpxE, LpxF, HP0350 and HP0851. Here, we report the physiological role of HP0851, renamed HupA, via multiple and complementary approaches ranging from a detailed biochemical characterization to the assessment of its effect on cell envelope metabolism and microbe-host interactions. HupA displays a dual function as being the main C55-PP pyrophosphatase (UppP) and phosphatidylglycerol phosphate phosphatase (PGPase). Although not essential in vitro, HupA was essential in vivo for stomach colonization. In vitro, the remaining UppP activity was carried out by LpxE in addition to its lipid A 1-phosphate phosphatase activity. Both HupA and LpxE have crucial roles in the biosynthesis of several cell wall polysaccharides and thus constitute potential targets for new therapeutic strategies.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Grant Information:
      R01 AI038576 United States AI NIAID NIH HHS; R01 AI129940 United States AI NIAID NIH HHS; T32 GM107004 United States GM NIGMS NIH HHS; U01 AI038576 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Bacterial Outer Membrane Proteins)
      0 (Carrier Proteins)
      0 (DNA-Binding Proteins)
      0 (Escherichia coli Proteins)
      0 (HupA protein, bacteria)
      0 (Polyisoprenyl Phosphates)
      0 (hupA protein, E coli)
      31867-59-1 (undecaprenyl pyrophosphate)
      EC 3.1.3.- (lipid phosphate phosphatase)
      EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
      EC 3.1.3.27 (phosphatidylglycerophosphatase)
      EC 3.1.3.4 (Phosphatidate Phosphatase)
      EC 3.6.1.- (Pyrophosphatases)
      J2VZ07J96K (Polymyxin B)
    • Publication Date:
      Date Created: 20190906 Date Completed: 20200207 Latest Revision: 20201213
    • Publication Date:
      20231215
    • Accession Number:
      PMC6748449
    • Accession Number:
      10.1371/journal.ppat.1007972
    • Accession Number:
      31487328