title: Direct targets of CodY in Staphylococcus aureus.
abstract: More than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide analysis of in vitro DNA binding. This analysis, which was confirmed for some genes by DNase I footprinting assays, revealed that CodY is a direct regulator of numerous transcription units associated with amino acid biosynthesis, transport of macromolecules, and virulence. The virulence genes regulated by CodY fell into three groups. One group was dependent on the Agr system for its expression; these genes were indirectly regulated by CodY through its repression of the agr locus. A second group was regulated directly by CodY. The third group, which includes genes for alpha-toxin and capsule synthesis, was regulated by CodY in two ways, i.e., by direct repression and by repression of the agr locus. Since S. aureus CodY was activated in vitro by the branched chain amino acids and GTP, CodY appears to link changes in intracellular metabolite pools with the induction of numerous adaptive responses, including virulence.
authors.affiliation: Department of Molecular Biology and Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
authors.forename: Charlotte D
authors.initials: CD
authors.lastname: Majerczyk
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dunman
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Luong
authors.forename: Chia Y
authors.initials: CY
authors.lastname: Lee
authors.forename: Marat R
authors.initials: MR
authors.lastname: Sadykov
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
authors.forename: Kip
authors.initials: K
authors.lastname: Bodi
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Sonenshein
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D018983:DNA Footprinting; D024202:Electrophoretic Mobility Shift Assay; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D018085:Regulon / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; C540555:CodY protein, Staphylococcus aureus; D012097:Repressor Proteins; C492107:SarA protein, Staphylococcus aureus; D015534:Trans-Activators