title: Opposing effects of aminocoumarins and fluoroquinolones on the SOS response and adaptability in Staphylococcus aureus.
abstract: OBJECTIVE
  RecA is the key enzyme involved in DNA repair, recombination and induction of the SOS response and is central to the development of antibiotic resistance. Here we assessed the interaction of two different gyrase inhibitors, ciprofloxacin (a fluoroquinolone) and novobiocin (an aminocoumarin), on RecA activity and the SOS response in Staphylococcus aureus.
  
  
  METHODS
  The influence of different gyrase inhibitors on the SOS response of S. aureus (including recA and lexA mutants) was analysed by northern blot analysis, real-time RT-PCR, western blot analysis and promoter activity assays. Recombination as well as mutation frequencies were determined for the different antibiotic combinations.
  
  
  RESULTS
  We verified that ciprofloxacin leads to RecA activation and therefore induction of the SOS response. In contrast, novobiocin treatment resulted in an inhibition of recA transcription independent of LexA. When novobiocin and ciprofloxacin were added simultaneously, recA was reduced to the same level as with novobiocin alone. In combination, novobiocin also partially reduces the ciprofloxacin-mediated induction of the LexA target gene umuC (error-prone polymerase). Apart from reducing recA and umuC expression, novobiocin also inhibited the frequency of recombination, mutation and the formation of non-haemolytic variants.
  
  
  CONCLUSIONS
  In summary, aminocoumarins inhibit recA expression in S. aureus and probably delay the process of developing antibiotic resistance and gene transfer. A clinical re-evaluation of these compounds as well as designing more applicable derivatives should be considered.
authors.affiliation: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Strasse-6, 72076 Tübingen,  Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Schröder
authors.forename: Christiane
authors.initials: C
authors.lastname: Goerke
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolz
mesh_terms: D049933:Aminocoumarins / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D024841:Fluoroquinolones / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D011938:Rec A Recombinases / Q000096:biosynthesis; D013014:SOS Response, Genetics / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D049933:Aminocoumarins; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011938:Rec A Recombinases