Mgr, a novel global regulator in Staphylococcus aureus.
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.
Luong
Thanh T
TT
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Newell
Steven W
SW
Lee
Chia Y
CY
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
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