title: Staphylococcus aureus CodY negatively regulates virulence gene expression.
abstract: CodY is a global regulatory protein that was first discovered in Bacillus subtilis, where it couples gene expression to changes in the pools of critical metabolites through its activation by GTP and branched-chain amino acids. Homologs of CodY can be found encoded in the genomes of nearly all low-G+C gram-positive bacteria, including Staphylococcus aureus. The introduction of a codY-null mutation into two S. aureus clinical isolates, SA564 and UAMS-1, through allelic replacement, resulted in the overexpression of several virulence genes. The mutant strains had higher levels of hemolytic activity toward rabbit erythrocytes in their culture fluid, produced more polysaccharide intercellular adhesin (PIA), and formed more robust biofilms than did their isogenic parent strains. These phenotypes were associated with derepressed levels of RNA for the hemolytic alpha-toxin (hla), the accessory gene regulator (agr) (RNAII and RNAIII/hld), and the operon responsible for the production of PIA (icaADBC). These data suggest that CodY represses, either directly or indirectly, the synthesis of a number of virulence factors of S. aureus.
authors.affiliation: Tufts University Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts 02111, USA.
authors.forename: Charlotte D
authors.initials: CD
authors.lastname: Majerczyk
authors.forename: Marat R
authors.initials: MR
authors.lastname: Sadykov
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Luong
authors.forename: Chia
authors.initials: C
authors.lastname: Lee
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Sonenshein
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D018441:Biofilms / Q000254:growth & development; D015153:Blotting, Western; D004912:Erythrocytes / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006461:Hemolysis; D009154:Mutation; D011817:Rabbits; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D014158:Transcription, Genetic / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins