title: Protein A gene expression is regulated by DNA supercoiling which is modified by the ArlS-ArlR two-component system of Staphylococcus aureus.
abstract: Bacterial pathogens such as Staphylococcus aureus undergo major physiological changes when they infect their hosts, requiring the coordinated regulation of gene expression in response to the stresses encountered. Several environmental factors modify the expression of S. aureus virulence genes. This report shows that the expression of spa (virulence gene encoding the cell-wall-associated protein A) is down-regulated by high osmolarity (1 M NaCl, 1 M KCl or 1 M sucrose) in the wild-type strain and upregulated by novobiocin (a DNA gyrase inhibitor that relaxes DNA). A gyrB142 allele corresponding to a double mutation in the B subunit of DNA gyrase relaxed DNA and consequently induced spa expression, confirming that spa expression is regulated by DNA topology. Furthermore, in the presence of novobiocin plus 1 M NaCl, a good correlation was observed between DNA supercoiling and spa expression. The ArlS-ArlR two-component system is involved in the expression of virulence genes such as spa. Presence of an arlRS deletion decreased the effect of DNA supercoiling modulators on spa expression, suggesting that active Arl proteins are necessary for the full effect of DNA gyrase inhibitors and high osmolarity on spa expression. Indeed, evidence is provided for a relationship between the arlRS deletion and topological changes in plasmid DNA.
authors.affiliation: Laboratoire des Listeria, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Fournier
authors.affiliation: Université Paris 7, UFR de Biochimie, 2 place Jussieu, 75005 Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Klier
mesh_terms: D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry; D004278:DNA, Superhelical / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D009675:Novobiocin / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D009997:Osmotic Pressure; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013205:Staphylococcal Protein A / Q000096:biosynthesis* / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism*; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C411334:ArlR protein, Staphylococcus aureus; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D013205:Staphylococcal Protein A; D037521:Virulence Factors; D009675:Novobiocin; D011494:Protein Kinases; C411333:ArlS protein, Staphylococcus aureus; D027081:DNA Gyrase