title: Mgr, a novel global regulator in Staphylococcus aureus.
abstract: The virulence determinants of Staphylococcus aureus are coordinately controlled by several unlinked chromosomal loci. Here, we report the identification of CYL5614, derived from strain Becker, with a mutation that affects the expression of type 8 capsular polysaccharide (CP8), nuclease, alpha-toxin, coagulase, protease, and protein A. This novel locus, named mgr, was linked by transposon Tn917 and mapped by three-factorial transduction crosses. The region containing the mgr locus was cloned and sequenced. Deletion mutagenesis and genetic complementation showed that the locus consisted of one gene, mgrA. Interestingly, mgrA-null mutants exhibited a phenotype opposite to that of CYL5614. This was due to a T-to-C mutation upstream of mgrA that resulted in a four- to eightfold increase in mgrA transcription in strain CYL5614. Thus, these results indicate that mgrA is an activator of CP8 and nuclease but a repressor of alpha-toxin, coagulase, protease, and protein A. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses showed that the mgr locus profoundly affected extracellular protein production, suggesting that the locus may regulate many other genes as well. The translated MgrA protein has a region of significant homology, which includes the helix-turn-helix DNA-binding motif, with the Escherichia coli MarR family of transcriptional regulators. Northern slot blot analyses suggested that mgr affected CP8, alpha-toxin, nuclease, and protein A at the transcriptional level.
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Luong
authors.forename: Steven W
authors.initials: SW
authors.lastname: Newell
authors.forename: Chia Y
authors.initials: CY
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D016667:Bacterial Capsules; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004251:DNA Transposable Elements / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D019077:Helix-Turn-Helix Motifs; D008969:Molecular Sequence Data; D009154:Mutation; D011135:Polysaccharides, Bacterial; D017422:Sequence Analysis, DNA; D013205:Staphylococcal Protein A / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D011135:Polysaccharides, Bacterial; D013205:Staphylococcal Protein A; C064836:capsular polysaccharide, type 8, Staphylococcus aureus; D010738:Type C Phospholipases