title: Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor.
abstract: BACKGROUND
  Streptococcus agalactiae (group B Streptococcus; GBS) is a significant bacterial pathogen of neonates and an emerging pathogen of adults. Though transcriptional regulators are abundantly encoded on the GBS genome, their role in GBS pathogenesis is poorly understood. The mtaR gene encodes a putative LysR-type transcriptional regulator that is critical for the full virulence of GBS. Previous studies have shown that an mtaR- mutant transports methionine at reduced rates and grows poorly in normal human plasma not supplemented with methionine. The decreased virulence of the mtaR mutant was correlated with a methionine transport defect; however, no MtaR-regulated genes were identified.
  
  
  RESULTS
  Microarray analysis of wild-type GBS and an mtaR mutant revealed differential expression of 12 genes, including 1 upregulated and 11 downregulated genes in the mtaR mutant. Among the downregulated genes, we identified a cluster of cotranscribed genes encoding a putative methionine transporter (metQ1NP) and peptidase (pdsM). The expression of four genes potentially involved in arginine transport (artPQ) and arginine biosynthesis (argGH) was downregulated and these genes localized to two transcriptional units. The virulence factor cspA, which encodes an extracellular protease, was downregulated. Additionally, the SAN_1255 locus, which putatively encodes a protein displaying similarity to plasminogen activators, was downregulated.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to describe the global influence of MtaR on GBS gene expression. This study implicates the metQ1NP genes as encoding the MtaR-regulated methionine transporter, which may provide a mechanistic explanation for the methionine-dependent growth defect of the mtaR mutant. In addition to modulating the expression of genes involved in metabolism and amino acid transport, inactivation of mtaR affected the expression of other GBS genes implicated in pathogenesis. These findings suggest the possibility that MtaR may play a multifaceted role in GBS pathogenesis by regulating the expression of numerous genes.
authors.affiliation: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, Louisiana 71130, USA. jbryan@lsuhsc.edu
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Bryan
authors.forename: Roxanne
authors.initials: R
authors.lastname: Liles
authors.forename: Urska
authors.initials: U
authors.lastname: Cvek
authors.forename: Marjan
authors.initials: M
authors.lastname: Trutschl
authors.forename: Daniel
authors.initials: D
authors.lastname: Shelver
mesh_terms: D001120:Arginine / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008715:Methionine / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012329:RNA, Bacterial / Q000235:genetics; D013292:Streptococcus agalactiae / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D014157:Transcription Factors; D037521:Virulence Factors; D001120:Arginine; D008715:Methionine