Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus

BMC Genomics

Christiane Wolz⁶  Kay Nieselt⁵  Guido Krupp⁴  Alexander Herbig⁵  Ludger Klein-Hitpass¹  Gabriella Marincola²  Jörg Bernhardt³  Wiebke Schröder⁶ 

[1] Institut für Zellbiologie, Universitätsklinikum Essen, Virchowstraße 173, 45122 Essen, Germany;Present address: Research Centre for Infectious Diseases ZINF, University of Wuerzburg, Josef Schneider Str.2/ D15, Wuerzburg, Germany;Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald, F.-L.-Jahn-Str. 15, Greifswald, Germany;AmpTec GmbH, Königstraße 4A, 22767 Hamburg, Germany;Centre for Bioinformatics Tübingen, University of Tübingen, Sand 14, 72076 Tübingen, Germany;Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany

关键词: Voronoi tree map;    Microarray;    Novobiocin;    Aminocoumarins;    Spacer;    arlR;    Gyrase;    Supercoiling;    Staphylococcus aureus;   

Others  :  1217455
DOI  :  10.1186/1471-2164-15-291

 received in 2013-08-23, accepted in 2014-03-17,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Schröder et al.; licensee BioMed Central Ltd.

【 图 表 】

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