A direct link between carbohydrate utilization and virulence in the major human pathogen group A
            <i>Streptococcus</i>

Shelburne, Samuel A.; Keith, David; Horstmann, Nicola; Sumby, Paul; Davenport, M.; Graviss, Edward A.; Brennan, Richard G.; Musser, James M.

doi:10.1073/pnas.0711767105

Cited by 182 publications

(267 citation statements)

References 35 publications

(47 reference statements)

Supporting

Mentioning

237

Contrasting

Order By: Relevance

“…TaqMan primer and probe sequences are listed in Table S1. The constitutively transcribed housekeeping gene proS was used as an internal control, similar to previously published quantitative RT-PCR analyses (Shelburne et al, 2008;Virtaneva et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

“…TaqMan quantitative RT-PCR was performed using an ABI 7500 Fast System (Applied Biosystems). Gene transcript levels of mutant and complemented strains were compared to parental strain MGAS2221 using the 2 {DDCt method as described previously (Shelburne et al, 2008). TaqMan primer and probe sequences are listed in Table S1.…”

Section: Methodsmentioning

confidence: 99%

“…(b) To assess whether modulation of transcript abundance following 4.5S RNA mutation is CovS-dependent we analysed transcripts from MGAS2221 (+vector), 2221D4.5S (+vector), 2221covS : : 7bp (+vector), 2221covS : : 7bp/D4.5S (+vector) and 2221covS : : 7bp/D4.5S (+p4.5S). Quantitative RT-PCR data were normalized to the transcript levels of the commonly used housekeeping gene proS (Graham et al, 2006;Reid et al, 2003;Shelburne et al, 2008;Sumby et al, 2005a). 430, spy0430.…”

Section: Contribution Of the 45s Rna To Gas Growth And Persistence Imentioning

confidence: 99%

See 2 more Smart Citations

The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence

2010

Self Cite

View full text Add to dashboard Cite

The signal recognition particle (SRP) is a ribonucleoprotein complex that targets proteins for secretion in a co-translational manner. While originally thought to be essential in all bacteria, recent data show that the SRP is dispensable in at least some streptococcal species. The SRP from the human pathogen group A Streptococcus (GAS, Streptococcus pyogenes) is predicted to be composed of protein Ffh and 4.5S RNA. Deletion of ffh alters the secretion of several GAS proteins, and leads to a severe reduction in virulence. Here, we report that mutation of the gene encoding 4.5S RNA results in phenotypes both similar to and distinct from that observed following ffh mutation. Similarities include a reduction in secretion of the haemolysin streptolysin O, and attenuation of virulence as assessed by a murine soft tissue infection model. Differences include a reduction in transcript levels for the genes encoding streptolysin O and NADglycohydrolase, and the reduced secretion of the SpeB protease. Several differences in transcript abundance between the parental and mutant strain were shown to be dependent on the sensorkinase-encoding gene covS. Using growth in human saliva as an ex vivo model of upper respiratory tract infection we identified that 4.5S RNA mutation leads to a 10-fold reduction in colony-forming units over time, consistent with the 4.5S RNA contributing to GAS growth and persistence during upper respiratory tract infections. Finally, we determined that the 4.5S RNA was essential for GAS to cause lethal infections in a murine bacteraemia model of infection. The data presented extend our knowledge of the contribution of the SRP to the virulence of an important Gram-positive pathogen.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Contribution Of the 45s Rna To Gas Growth And Persistence Imentioning

confidence: 99%

See 1 more Smart Citation

The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence

2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…The CcpA⅐Hpr-Ser(P)-46 complex has an increased affinity for particular cis-acting sequences, termed catabolite-responsive element (cre) sequences, and thereby represses or enhances gene expression depending on the position of the cre in relation to the operator sequence (3,4). In a number of Gram-positive pathogens such as Bacillus anthracis (5), Clostridium difficile (6), Staphylococcus aureus (7), Staphylococcus epidermidis (8), Streptococcus pneumoniae (9), and Streptococcus pyogenes (10), CcpA is also involved in the regulation of virulence determinants.…”

mentioning

confidence: 99%

A Novel Mode of Regulation of the Staphylococcus aureus Catabolite Control Protein A (CcpA) Mediated by Stk1 Protein Phosphorylation

Leiba

Hartmann

Cluzel

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The catabolite control protein A (CcpA) plays an important role in Staphylococcus aureus virulence, biofilm formation, and central metabolism. Results: Phosphorylation of CcpA negatively affects its DNA binding activity and thus the expression of its target genes. Conclusion: CcpA activity is modulated by Stk1 phosphorylation. Significance: This study highlights that phosphorylation of CcpA represents a novel regulatory control mechanism for this major transcriptional factor.

show abstract

“…Therefore, investigation of the regulatory mechanism of sag SCC transcription will also be important in evaluating the exact virulence determinants of b-SCC strains. In S. pyogenes, the production of SLS has been reported to be regulated by several mechanisms at the transcription level of the sag operon, such as the transcriptional regulator CovRS (alternative name, CsrRS) system (Engleberg et al, 2004;Federle et al, 1999;Graham et al, 2002), CCR (Kinkel & McIver, 2008;Shelburne et al, 2008, Kietzman & Caparon, 2010 and LacD.1 (Kinkel & McIver, 2008). SLS production in Streptococcus iniae has also been shown to be regulated by the two-component system sivS/R (Bolotin et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

A streptolysin S homologue is essential for β-haemolytic Streptococcus constellatus subsp. constellatus cytotoxicity

et al. 2014

View full text Add to dashboard Cite

Streptococcus constellatus is a member of the Anginosus group streptococci (AGS) and primarily inhabits the human oral cavity. S. constellatus is composed of three subspecies: S. constellatus subsp. constellatus (SCC), S. constellatus subsp. pharyngis and the newly described subspecies S. constellatus subsp. viborgensis. Although previous studies have established that SCC contains b-haemolytic strains, the factor(s) responsible for b-haemolysis in b-haemolytic SCC (b-SCC) has yet to be clarified. Recently, we discovered that a streptolysin S (SLS) homologue is the b-haemolytic factor of b-haemolytic Streptococcus anginosus subsp. anginosus (b-SAA), another member of the AGS. Furthermore, because previous studies have suggested that other AGS species, except for Streptococcus intermedius, do not possess a haemolysin(s) belonging to the family of cholesterol-dependent cytolysins, we hypothesized that, as with b-SAA, the SLS homologue is the b-haemolytic factor of b-SCC, and therefore aimed to investigate and characterize the haemolytic factor of b-SCC in the present study. PCR amplification revealed that all of the tested b-SCC strains were positive for the sagA homologue of SCC (sagA SCC ). Further investigations using b-SCC strain W277 were conducted to elucidate the relationship between sagA SCC and b-haemolysis by constructing sagA SCC deletion mutants, which completely lost bhaemolytic activity. This loss of b-haemolytic activity was restored by trans-complementation of sagA SCC . Furthermore, a co-cultivation assay established that the cytotoxicity of b-SCC was clearly dependent on the presence of sagA SCC . These results demonstrate that sagA SCC is the factor responsible for b-SCC b-haemolysis and cytotoxicity. INTRODUCTIONAnginosus group streptococci (AGS) are commensal bacteria in the human oral cavity. Current classification assigns AGS to three species, including five subspecies (Jensen et al., 2013): Streptococcus anginosus subsp. anginosus (SAA), S. anginosus subsp. whileyi (SAW), Streptococcus constellatus Abbreviations: AGS, Anginosus group streptococci; CSP, competence-stimulating peptide; erm, erythromycin resistance gene cassette; GAS, group A streptococci; GBS, group B streptococci; PGS, Pyogenic group streptococci; SAA, Streptococcus anginosus subsp. anginosus; SAW, Streptococcus anginosus subsp. whileyi; SCC, Streptococcus constellatus subsp. constellatus; SCP, Streptococcus constellatus subsp. pharyngis; SCV, Streptococcus constellatus subsp. viborgensis; SLS, streptolysin S.The GenBank/EMBL/DDBJ accession numbers for the sag operon homologue from b-haemolytic SCC strain W277, the sagA homologues from bhaemolytic SCC strains HW74 and 1340, and the sag operon homologues from the SCP type strain MM9889a T (5SK1060 T ), the SAW strain MAS624 and the SCV type strain SK1359 T are AB389362, AB389363, AB389364, AB389365, AB389366 and AB860419, respectively. (2014), 160, 980-991 Microbiology

show abstract

A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus

Abstract: The authors note that due to a printer's error, on page 4460, Fig. 2 appears incorrectly in part. The middle and bottom panels were transposed. The corrected figure and its legend appear below. MGAS5005∆ccpA comp∆ccpA

Cited by 182 publications

References 35 publications

The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence

The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence

A Novel Mode of Regulation of the Staphylococcus aureus Catabolite Control Protein A (CcpA) Mediated by Stk1 Protein Phosphorylation

A streptolysin S homologue is essential for β-haemolytic Streptococcus constellatus subsp. constellatus cytotoxicity

Contact Info

Product

Resources

About