title: Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus.
abstract: BACKGROUND
  It has been shown previously that aminocoumarin antibiotics such as novobiocin lead to immediate downregulation of recA expression and thereby inhibit the SOS response, mutation frequency and recombination capacity in Staphylococcus aureus. Aminocoumarins function by inhibiting the ATPase activity of DNA gyrase subunit B with a severe impact on DNA supercoiling.
  
  
  RESULTS
  Here, we have analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. Using a novobiocin-resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and northern blot hybridisation revealed that the expression levels of a distinct set of genes were increased (e.g., recF-gyrB-gyrA, the rib operon and the ure operon) or decreased (e.g., arlRS, recA, lukA, hlgC and fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the level of supercoiling in S. aureus. Thus, downregulation of arlRS might partially compensate for the relaxing effect of novobiocin. Global analysis and gene mapping of supercoiling-sensitive genes did not provide any indication that they are clustered in the genome. Promoter fusion assays confirmed that the responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location.
  
  
  CONCLUSIONS
  The results indicate that the molecular properties of a given promoter, rather than the chromosomal topology, dictate the responsiveness to changes in supercoiling in the pathogen Staphylococcus aureus.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Schröder
authors.forename: Jörg
authors.initials: J
authors.lastname: Bernhardt
authors.forename: Gabriella
authors.initials: G
authors.lastname: Marincola
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: Alexander
authors.initials: A
authors.lastname: Herbig
authors.forename: Guido
authors.initials: G
authors.lastname: Krupp
authors.forename: Kay
authors.initials: K
authors.lastname: Nieselt
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany. christiane.wolz@med.uni-tuebingen.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolz
mesh_terms: D049933:Aminocoumarins / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D027081:DNA Gyrase / Q000378:metabolism; D004278:DNA, Superhelical / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D016680:Genome, Bacterial; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D049933:Aminocoumarins; D000970:Antineoplastic Agents; C411334:ArlR protein, Staphylococcus aureus; D001426:Bacterial Proteins; D004278:DNA, Superhelical; D011938:Rec A Recombinases; D027081:DNA Gyrase
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