title: Spx mediates oxidative stress regulation of the methionine sulfoxide reductases operon in Bacillus subtilis.
abstract: BACKGROUND
  All aerobically grown living cells are exposed to oxidative damage by reactive oxygen species (ROS). A major damage by ROS to proteins is caused by covalent modifications of methionine residues giving methionine sulfoxide (Met-SO). Methionine sulfoxide reductases are enzymes able to regenerate methionine and restore protein function after oxidative damage.
  
  
  RESULTS
  We characterized the methionine sulfoxide reductase genes msrA and msrB in Bacillus subtilis, forming an operon transcribed from a single sigma A-dependent promoter. The msrAB operon was specifically induced by oxidative stress caused by paraquat (PQ) but not by H2O2. Spx, a global oxidative stress regulator in B. subtilis, is primarily responsible for this PQ-specific induction of msrAB expression. In support of this finding, an spx deletion mutant is extremely sensitive to PQ, and increased expression of msrA was identified in a clpX mutant in which Spx accumulated. However, the Spx effect was also visible under conditions where the protein did not accumulate (PQ treatment), suggesting a specific molecular effect at the level of the Spx protein. Indeed, the CXXC motif of Spx was found essential for its function in the PQ-specific induction of msrAB expression. PQ caused a modification of Spx requiring at least one of the cysteines of the CXXC motif of Spx. The PQ modified form of Spx showed a dynamic change in vivo.
  
  
  CONCLUSIONS
  The Spx mediated PQ-specific regulation pathway of the msrAB operon in B. subtilis is reported. Our results suggest that PQ induced the expression of msrAB partially through an oxidation on Spx via modification of its CXXC motif.
authors.affiliation: Institut Pasteur, Unité de Génétique des Génomes Bactériens, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France. cyou@physics.ucsd.edu
authors.forename: CongHui
authors.initials: C
authors.lastname: You
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sekowska
authors.forename: Olivera
authors.initials: O
authors.lastname: Francetic
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martin-Verstraete
authors.forename: YiPing
authors.initials: Y
authors.lastname: Wang
authors.forename: Antoine
authors.initials: A
authors.lastname: Danchin
mesh_terms: D020816:Amino Acid Motifs / Q000187:drug effects; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005809:Genes, Regulator / Q000187:drug effects; D008715:Methionine / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases; D009876:Operon / Q000187:drug effects; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010269:Paraquat / Q000494:pharmacology; D011401:Promoter Regions, Genetic
chemical_list: D001426:Bacterial Proteins; D008715:Methionine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D010269:Paraquat