Role of
            <i>Streptococcus pyogenes</i>
            Two-Component Response Regulators in the Temporal Control of Mga and the Mga-Regulated Virulence Gene
            <i>emm</i>

Ribardo, Deborah A.; Lambert, Thomas; McIver, Kevin S.

doi:10.1128/iai.72.6.3668-3673.2004

Cited by 22 publications

(23 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the trxSR coding regions of SF370 and MGAS5005 are identical and TrxR represses the Mga regulon in MGAS5005, trxR was not identified as necessary for expression of the Mga-regulated gene emm in a previous mutational analysis of the 12 nonessential TCS response regulators in SF370 (34). Additional real-time RT-PCR and Northern studies of the M1 strain SF370 trxR mutant confirmed these results for several other Mga-regulated genes (data not shown).…”

Section: Vol 76 2008supporting

confidence: 70%

“…trxR (M5005_Spy_1305) was inactivated in strain MGAS5005 using the temperature-sensitive integration method as previously described (32) to produce MGAS5005.trxR. Briefly, plasmid p233-10R (34) was electroporated into MGAS5005, followed by passage at 30°C with erythromycin selection. To allow for integration of the plasmid, cells were passaged at 37°C under erythromycin selection.…”

Section: Methodsmentioning

confidence: 99%

“…In a previous study, we constructed mutations in the 12 nonessential S. pyogenes TCS (Spt) response regulator genes in the serotype M1 strain SF370 (34). One of these TCS response regulator mutants, originally called Spt10SR (TCS-10; Spy1587-Spy1588) and here renamed GAS two-component regulatory system X or trxSR, shows homology to the hk07-rr07 TCS in S. pneumoniae (20,46), which is essential for full virulence in several models of pneumococcal infection.…”

mentioning

confidence: 99%

See 2 more Smart Citations

TrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus

et al. 2008

Self Cite

View full text Add to dashboard Cite

Coordinate regulation of virulence factors by the group A streptococcus (GAS) Streptococcus pyogenes is important in this pathogen's ability to cause disease. To further elucidate the regulatory network in this human pathogen, the CovR-repressed two-component system (TCS) trxSR was chosen for further analysis based on its homology to a virulence-related TCS in Streptococcus pneumoniae. In a murine skin infection model, an insertion mutation in the response regulator gene, trxR, led to a significant reduction in lesion size, lesion severity, and lethality. Curing the trxR mutation restored virulence comparable to the wild-type strain. The trxSR operon was defined in vivo, and CovR was found to directly repress its promoter in vitro. DNA microarray analysis established that TrxR activates transcription of Mga-regulated virulence genes, which may explain the virulence attenuation of the trxR mutant. This regulation appears to occur by activation of the mga promoter, Pmga, as demonstrated by analysis of a luciferase reporter fusion. Complementation of the trxR mutant with trxR on a plasmid restored expression of Mga regulon genes and restored virulence in the mouse model to wild-type levels. TrxR is the first TCS shown to regulate Mga expression. Because it is CovR repressed, TrxR defines a new pathway by which CovR can influence Mga to affect pathogenesis in the GAS.

show abstract

Section: Vol 76 2008supporting

confidence: 70%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

TrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Of the many genes present among S. pyogenes that encode regulators of transcription (20,57), two loci are known to exhibit extensive genetic diversity within the S. pyogenes population. These are mga and rofA/nra, encoding the "standalone" response regulators Mga and RofA/Nra, for which the interacting sensory elements remain unknown (36,50). The mga and rofA/nra loci are positioned ϳ300 kb apart on the S. pyogenes genome (see Fig.…”

Section: Resultsmentioning

confidence: 99%

Evolution of Transcription Regulatory Genes Is Linked to Niche Specialization in the Bacterial Pathogen Streptococcus pyogenes

et al. 2005

View full text Add to dashboard Cite

Streptococcus pyogenes is a highly prevalent bacterial pathogen, most often giving rise to superficial infections at the throat or skin of its human host. Three genotype-defined subpopulations of strains exhibiting strong tropisms for either the throat or skin (specialists) or having no obvious tissue site preference (generalists) are recognized. Since the microenvironments at the throat and skin are distinct, the signal transduction pathways leading to the control of gene expression may also differ for throat versus skin strains of S. pyogenes. Two loci (mga and rofA/nra) encoding global regulators of virulence gene expression are positioned 300 kb apart on the genome; each contains alleles forming two major sequence clusters of ϳ25 to 30% divergence that are under balancing selection. Strong linkage disequilibrium is observed between sequence clusters of the transcription regulatory loci and the subpopulations of throat and skin specialists, against a background of high recombination rates among housekeeping genes. A taxonomically distinct commensal species (Streptococcus dysgalactiae subspecies equisimilus) shares highly homologous rof alleles. The findings provide strong support for a mechanism underlying niche specialization that involves orthologous replacement of regulatory genes following interspecies horizontal transfer, although the directionality of gene exchange remains unknown.

show abstract

“…TCSs regulate multiple unlinked chromosomal genes and control coordinated expression of genes encoding virulence factors, such as toxins, degradative enzymes, and immune-modulating molecules, in response to environmental stimuli. Since 2001, each of the 13 TCSs has been studied by genome-wide analyses to some degree, many in detail (58)(59)(60)(61)(62). Similarly, there are more than 100 putative stand-alone transcriptional regulators encoded within the GAS genome, only a few of which had been identified before the availability of a genome sequence.…”

Section: Expanded Understanding Of Virulence Factor Regulation Pathwaysmentioning

confidence: 99%

A decade of molecular pathogenomic analysis of group A Streptococcus

Musser¹,

Shelburne²

2009

J. Clin. Invest.

View full text Add to dashboard Cite

Molecular pathogenomic analysis of the human bacterial pathogen group A Streptococcus has been conducted for a decade. Much has been learned as a consequence of the confluence of low-cost DNA sequencing, microarray technology, high-throughput proteomics, and enhanced bioinformatics. These technical advances, coupled with the availability of unique bacterial strain collections, have facilitated a systems biology investigative strategy designed to enhance and accelerate our understanding of disease processes. Here, we provide examples of the progress made by exploiting an integrated genome-wide research platform to gain new insight into molecular pathogenesis. The studies have provided many new avenues for basic and translational research.

show abstract

Role of Streptococcus pyogenes Two-Component Response Regulators in the Temporal Control of Mga and the Mga-Regulated Virulence Gene emm

Cited by 22 publications

References 24 publications

TrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus

TrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus

Evolution of Transcription Regulatory Genes Is Linked to Niche Specialization in the Bacterial Pathogen Streptococcus pyogenes

A decade of molecular pathogenomic analysis of group A Streptococcus

Contact Info

Product

Resources

About