<i>rgf</i>
            Encodes a Novel Two-Component Signal Transduction System of
            <i>Streptococcus agalactiae</i>

Spellerberg, Barbara; Rozdzinski, Eva; Martin, Simone; Weber-Heynemann, Josefine; Lütticken, Rudolf

doi:10.1128/iai.70.5.2434-2440.2002

Cited by 52 publications

(71 citation statements)

References 31 publications

(24 reference statements)

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“…Twocomponent regulators as part of an operon with additional genes can be seen in quorum-sensing systems, such as agr (21). Recently, the regulatory operon rgf was shown to modulate genes involved in adhesion and virulence in Streptococcus agalactiae (37). rgf shows the same gene organization as the sae operon: four ORFs which are cotranscribed and predicted to encode one unknown protein, and one putative peptide with a signal sequence followed by a typical response regulator and a histidine kinase.…”

Section: Discussionmentioning

confidence: 99%

Molecular Architecture of the Regulatory Locus sae of Staphylococcus aureus and Its Impact on Expression of Virulence Factors

Steinhuber

Goerke

Bayer³

et al. 2003

J Bacteriol

119

168

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We characterized the sae operon, a global regulator for virulence gene expression in Staphylococcus aureus. A Tn917 sae mutant was obtained by screening a Tn917 library of the agr mutant ISP479Mu for clones with altered hemolytic activity. Sequence analysis of the sae operon revealed two additional open reading frames (ORFs) (ORF3 and ORF4) upstream of the two-component regulatory genes saeR and saeS. Four overlapping sae-specific transcripts (T1 to T4) were detected by Northern blot analysis, and the transcriptional initiation points were mapped by primer extension analysis. The T1, T2, and T3 mRNAs are probably terminated at the same stem-loop sequence downstream of saeS. The T1 message (3.1 kb) initiates upstream of ORF4, T2 (2.4 kb) initiates upstream of ORF3, and T3 (2.0 kb) initiates in front of saeR. T4 (0.7 kb) represents a monocistronic mRNA encompassing ORF4 only. sae-specific transcripts were detectable in all of the 40 different clinical S. aureus isolates investigated. Transcript levels were at maximum during the post-exponential growth phase. The sae mutant showed a significantly reduced rate of invasion of human endothelial cells, consistent with diminished transcription and expression of fnbA. The expression of type 5 capsular polysaccharide is activated in the sae mutant of strain Newman, as shown by immunofluorescence and promoter-reporter fusion experiments. In summary, the sae operon constitutes a four-component regulator system which acts on virulence gene expression in S. aureus.

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Section: Discussionmentioning

confidence: 99%

Molecular Architecture of the Regulatory Locus sae of Staphylococcus aureus and Its Impact on Expression of Virulence Factors

Steinhuber

Goerke

Bayer³

et al. 2003

J Bacteriol

119

168

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“…At present, the molecu-lar basis for the oligopeptide permease-dependent regulation of fbsA expression in S. agalactiae remains unknown. However, a putative quorum-sensing system was recently identified in S. agalactiae O90R (61). Interestingly, the inactivation of this quorum-sensing system also changed the fibrinogen-binding properties of the resultant mutant.…”

Section: Discussionmentioning

confidence: 99%

Relevance of Peptide Uptake Systems to the Physiology and Virulence of Streptococcus agalactiae

et al. 2004

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Streptococcus agalactiae is a major cause of invasive infections in human newborns. To satisfy its growth requirements, S. agalactiae takes up 9 of the 20 proteinogenic amino acids from the environment. Defined S. agalactiae mutants in one or several of four putative peptide permease systems were constructed and tested for peptide uptake, growth in various media, and expression of virulence traits. Oligopeptide uptake by S. agalactiae was shown to be mediated by the ABC transporter OppA1-F, which possesses two substrate-binding proteins (OppA1 and OppA2) with overlapping substrate specificities. Dipeptides were found to be taken up in parallel by the oligopeptide permease OppA1-F, by the dipeptide ABC transporter DppA-E, and by the dipeptide symporter DpsA. Reverse transcription-PCR analysis revealed a polycistronic organization of the genes oppA1-F and dppA-E and a monocistronic organization of dpsA in S. agalactiae. The results of quantitative real-time PCR revealed a medium-dependent expression of the operons dppA-E and oppA1-F in S. agalactiae. Growth of S. agalactiae in human amniotic fluid was shown to require an intact dpsA gene, indicating an important role of DpsA during the infection of the amniotic cavity by S. agalactiae. Deletion of the oppB gene reduced the adherence of S. agalactiae to epithelial cells by 26%, impaired its adherence to fibrinogen and fibronectin by 42 and 33%, respectively, and caused a 35% reduction in expression of the fbsA gene, which encodes a fibrinogen-binding protein in S. agalactiae. These data indicate that the oligopeptide permease is involved in modulating virulence traits and virulence gene expression in S. agalactiae.Streptococcus agalactiae has a limited capacity to synthesize amino acids and must acquire from the environment 9 of the 20 proteinogenic amino acids for growth (38). The amino acid requirements of S. agalactiae can be satisfied by the uptake of peptides, which are cleaved in the cytoplasm to their respective amino acids (69, 70). In microorganisms, two different peptide uptake systems have been described (23, 41). The most common peptide transporters are binding-protein-dependent permeases, consisting of multiple components, belonging to the ATP-binding cassette (ABC) transporter superfamily (24). The process of peptide transport by ABC transporters involves the extracytoplasmic binding of the substrate by a substrate-binding protein, transfer of the substrate to two membrane-integrated permeases for translocation across the cytoplasmic membrane, and ATP hydrolysis by one or two proteins located on the cytoplasmic side of the membrane (24). In numerous bacteria, the uptake of di-and oligopeptides is mediated by these ABC transporters (41). In contrast, some microorganisms take up diand/or tripeptides by single proteins with similarity to eukaryotic peptide transport proteins of the PRT family (62). These bacterial permeases use the proton motive force across the cytoplasmic membrane for the uptake of peptides (23, 37). They exhibit a broad substrate spec...

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“…Another two-component system in GBS was identified in a screen for mutants defective in fibrinogen binding. The RgfA/RgfC response regulator and histidine kinase appear to regulate expression of C5a peptidase (31). In addition to these two typical bacterial histidine kinase/phosphoregulator systems, Rajagopal et al described a eukaryotic type serine-threonine kinase coupled to a cognate phosphatase (25).…”

Section: Group B Streptococcus (Gbs) (Or Streptococcus Agalactiae)mentioning

confidence: 99%

Regulation of Virulence by a Two-Component System in Group B Streptococcus

et al. 2005

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Group B Streptococcus (GBS) is frequently carried in the gastrointestinal or genitourinary tract as a commensal organism, yet it has the potential to cause life-threatening infection in newborn infants, pregnant women, and individuals with chronic illness. Regulation of virulence factor expression may affect whether GBS behaves as an asymptomatic colonizer or an invasive pathogen, but little is known about how such factors are controlled in GBS. We now report the characterization of a GBS locus that encodes a two-component regulatory system similar to CsrRS (or CovRS) in Streptococcus pyogenes. Inactivation of csrR, encoding the putative response regulator, in two unrelated wild-type strains of GBS resulted in a marked increase in production of beta-hemolysin/cytolysin and a striking decrease in production of CAMP factor, an unrelated cytolytic toxin. Quantitative RNA hybridization experiments revealed that these two phenotypes were associated with a marked increase and decrease in expression of the corresponding genes, cylE and cfb, respectively. The CsrR mutant strains also displayed increased expression of scpB encoding C5a peptidase. Similar, but less marked, changes in gene expression were observed in CsrS (putative sensor component) mutants, evidence that CsrR and CsrS constitute a functional two-component system. Experimental infection studies in mice demonstrated reduced virulence of both CsrR and CsrS mutant strains relative to the wild type. Together, these results indicate that CsrRS regulates expression of multiple GBS virulence determinants and is likely to play an important role in GBS pathogenesis. Group B Streptococcus (GBS) (or Streptococcus agalactiae)is an important cause of invasive infection in newborn infants, in women around the time of childbirth, and in older individuals with underlying chronic illnesses (28). Although GBS has the capacity to produce life-threatening infection in susceptible hosts, more often it behaves as a harmless commensal organism. Surveys of asymptomatic volunteers have demonstrated that GBS colonizes the vagina and/or rectum of one-third to one-half of healthy women (12). Because GBS encounters a variety of environmental conditions in the varied niches it occupies, the organism's survival in the human host may be enhanced by its ability to perceive changes in the external milieu and to adapt by altering expression of specific genes. This dynamic adaptation of GBS to the human host is likely to involve one or more regulatory systems that control expression of bacterial factors important in adhesion, nutrient acquisition, resistance to host immune effectors, and under certain circumstances, invasion of host tissues.One mechanism for adaptation to changing environments is through two-component regulatory systems, a family of proteins that are widely distributed among many bacterial genera (20,32). Two-component systems allow sensing of specific environmental signals through a sensor histidine kinase that is usually associated with the cell membrane. In the basic mode...

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rgf Encodes a Novel Two-Component Signal Transduction System of Streptococcus agalactiae

Cited by 52 publications

References 31 publications

Molecular Architecture of the Regulatory Locus sae of Staphylococcus aureus and Its Impact on Expression of Virulence Factors

Molecular Architecture of the Regulatory Locus sae of Staphylococcus aureus and Its Impact on Expression of Virulence Factors

Relevance of Peptide Uptake Systems to the Physiology and Virulence of Streptococcus agalactiae

Regulation of Virulence by a Two-Component System in Group B Streptococcus

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