title: BcrC from Bacillus subtilis acts as an undecaprenyl pyrophosphate phosphatase in bacitracin resistance.
abstract: Overexpression of the BcrC(Bs) protein, formerly called YwoA, in Escherichia coli or in Bacillus subtilis allows these bacteria to stand higher concentrations of bacitracin. It was suggested that BcrC(Bs) was a membrane-spanning domain of an ATP binding cassette (ABC) transporter involved in bacitracin resistance. However, we hypothesized that this protein has an undecaprenyl pyrophosphate (UPP) phosphatase activity able to compete with bacitracin for UPP. We found that overexpression of a recombinant His6-BcrC(Bs) protein in E. coli (i) increased the resistance of the cells to bacitracin and (ii) increased UPP phosphatase activity in membrane preparations by 600-fold. We solubilized and prepared an electrophoretically pure protein exhibiting a strong UPP phosphatase activity. BcrC(Bs), which belongs to the type 2 phosphatidic acid phosphatase (PAP2) phosphatase superfamily (PF01569), differs totally from the already known BacA UPP phosphatase from E. coli, a member of the PF02673 family of the Protein family (Pfam) database. Thus, BcrC(Bs) and its orthologs form a new class of proteins within the PAP2 phosphatase superfamily, and likely all of them share a UPP phosphatase activity.
authors.affiliation: Laboratoire de Chimie Bactérienne, Institut de Biologie Structurale et Microbiologie, Bātiment 430, 91405 Orsay Cedex, France.
authors.forename: Remi
authors.initials: R
authors.lastname: Bernard
authors.forename: Meriem
authors.initials: M
authors.lastname: El Ghachi
authors.forename: Dominique
authors.initials: D
authors.lastname: Mengin-Lecreulx
authors.forename: Marc
authors.initials: M
authors.lastname: Chippaux
authors.forename: François
authors.initials: F
authors.lastname: Denizot
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism* / Q000502:physiology*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000378:metabolism*; D001414:Bacitracin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry; D001483:Base Sequence; D003001:Cloning, Molecular; D019295:Computational Biology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D017353:Gene Deletion; D008969:Molecular Sequence Data; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D011485:Protein Binding; D011755:Pyrophosphatases / Q000378:metabolism* / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D018759:Adrenergic Uptake Inhibitors; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011106:Polyisoprenyl Phosphates; C121796:bacitracin permease; D001414:Bacitracin; C088139:undecaprenyl pyrophosphate; D012110:Reserpine; D010744:Phosphoric Monoester Hydrolases; D011755:Pyrophosphatases; C503879:undecaprenyl pyrophosphate phosphatase