Open AccessHupA, the main undecaprenyl pyrophosphate and phosphatidylglycerol phosphate phosphatase in Helicobacter pylori is essential for colonization of the stomach
Author(s) -
Elise Gasiorowski,
Rodolphe Auger,
Xudong Tian,
Samia Hicham,
Chantal Ecobichon,
Sophie Roure,
Martin V. Douglass,
M. Stephen Trent,
Dominique MenginLecreulx,
Thierry Touzé,
Ivo Gomperts Boneca
Publication year - 2019
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1007972
Subject(s) - biochemistry , phosphatase , phosphatidic acid , biology , dephosphorylation , phosphatidylglycerol , cell envelope , microbiology and biotechnology , chemistry , enzyme , phospholipid , membrane , escherichia coli , phosphatidylcholine , gene
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 (C 55 -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 (C 55 -PP) form. Thus, C 55 -P is generated through the dephosphorylation of C 55 -PP, itself arising from either de novo synthesis or recycling. Two types of integral membrane C 55 -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 C 55 -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.