Role of mga in growth phase regulation of virulence genes of the group A streptococcus

McIver, Kevin S.; Scott, June R.

doi:10.1128/jb.179.16.5178-5187.1997

Cited by 129 publications

(150 citation statements)

References 66 publications

(66 reference statements)

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“…While emm gene expression is known to be under the control of the trans-acting regulator mga (Caparon & Scott, 1987;McIver & Scott, 1997), this regulator has no effect on ska or speB expression. Expression of speB is controlled by rgg and this regulator has no effect on emm or ska expression (Chaussee et al, 1999(Chaussee et al, , 2001Lyon et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activity

2004

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The plasminogen activator streptokinase has been proposed to be a key component of a complex mechanism that promotes skin invasion by Streptococcus pyogenes. This study was designed to compare ska gene message and protein levels in wild-type M1 serotype isolate 1881 and a more invasive variant recovered from the spleen of a lethally infected mouse. M1 isolates selected for invasiveness demonstrated enhanced levels of active plasminogen activator activity in culture. This effect was due to a combination of increased expression of the ska gene and decreased expression of the speB gene. The speB gene product, SpeB, was found to efficiently degrade streptokinase in vitro.

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Section: Discussionmentioning

confidence: 99%

Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activity

2004

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“…Mga is a trans-acting positive transcriptional regulator of genes encoding the virulence factors M protein, C5a peptidase, streptococcal inhibitor of complement, and streptococcal collagen-like protein 1 (29,(34)(35)(36). Mga influences gene transcription in the exponential phase, but not in the stationary phase, and its action is linked to Fig.…”

Section: Human Immune Response To Recombinant Protein Fragmentsmentioning

confidence: 99%

Multilocus analysis of extracellular putative virulence proteins made by group A Streptococcus: Population genetics, human serologic response, and gene transcription

Reid

Green

Buss

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Species of pathogenic microbes are composed of an array of evolutionarily distinct chromosomal genotypes characterized by diversity in gene content and sequence (allelic variation). The occurrence of substantial genetic diversity has hindered progress in developing a comprehensive understanding of the molecular basis of virulence and new therapeutics such as vaccines. To provide new information that bears on these issues, 11 genes encoding extracellular proteins in the human bacterial pathogen group A Streptococcus identified by analysis of four genomes were studied. Eight of the 11 genes encode proteins with a LPXTG(L) motif that covalently links Gram-positive virulence factors to the bacterial cell surface. Sequence analysis of the 11 genes in 37 geographically and phylogenetically diverse group A Streptococcus strains cultured from patients with different infection types found that recent horizontal gene transfer has contributed substantially to chromosomal diversity. Regions of the inferred proteins likely to interact with the host were identified by molecular population genetic analysis, and Western immunoblot analysis with sera from infected patients confirmed that they were antigenic. Real-time reverse transcriptase-PCR (TaqMan) assays found that transcription of six of the 11 genes was substantially up-regulated in the stationary phase. In addition, transcription of many genes was influenced by the covR and mga trans-acting gene regulatory loci. Multilocus investigation of putative virulence genes by the integrated approach described herein provides an important strategy to aid microbial pathogenesis research and rapidly identify new targets for therapeutics research.

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“…S. pyogenes JRS519 is a ⌬mga kanamycin-resistant derivative of the serotype M6 strain JRS4 (17,24). The S. pyogenes vectors for integration (VIT) strain RTG229 is a derivative of JRS4 (7).…”

Section: Methodsmentioning

confidence: 99%

“…A plasmid containing both the Mga-like regulator gene dmgB and the linked DmgB-regulated gene demB from S. dysgalactiae subsp. dysgalactiae (28) under the native PdmgB promoter were introduced into the ⌬mga M6 GAS strain JRS519 (17). Northern analysis was then used to monitor DmgB-mediated activation of demB in the ⌬mga GAS background (Fig.…”

Section: Vol 188 2006 Functional Residues Of Mga 869mentioning

confidence: 99%

“…Although the mechanism by which Mga can respond to environmental signals remains undefined, it has been shown to positively activate its own expression (18,19) along with the expression of other genes within its regulon in response to increased CO 2 levels, body temperature, and exponential-phase growth (4,15,17,22). In the GAS, the mga regulon is composed of genes important for colonization and immune evasion, such as those encoding the antiphagocytic M protein (emm), an immunoglobulin-binding protein (mrp), a collagen-like protein (scl), and a C5a peptidase (scpA).…”

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Domains Required for Transcriptional Activation Show Conservation in the Mga Family of Virulence Gene Regulators

Vahling

McIver

2006

J Bacteriol

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Mga, or the multigene regulator of the group A streptococcus (GAS) (Streptococcus pyogenes), is a transcriptional regulator of virulence genes important for colonization and immune evasion. All serotypes of the GAS possess one of two divergent mga alleles (mga-1 or mga-2), and orthologues of Mga have also been identified in other pathogenic streptococci. To date, the only functional motifs established within Mga are two aminoterminal DNA-binding domains (HTH-3 and HTH-4). To uncover novel domains, a random mutagenesis screen using an M6 Mga (mga-1) was undertaken to find mutations leading to a defect in transcriptional activation of the Mga-regulated emm gene. In addition to mutations in the established DNA-binding domains, the screen also revealed mutations in a region conserved among several Mga orthologues. Alanine scanning helped resolve the boundaries of this conserved Mga domain (CMD-1) spanning from residues 10 to 15 of the protein, with the two flanking amino acid residues likely involved in protein stability. Transcriptional reporter analyses demonstrated the importance of CMD-1 for activation of Pemm and autoactivation of Pmga in the serotype M6 Mga. Mutational analyses showed that both CMD-1 and HTH-4 are also necessary for activation of the promoter target Pmrp in a divergent serotype M4 Mga (mga-2), suggesting a conserved functionality. However, in contrast to M6, the M4 Mga mutants did not show a defect in autoregulation. Mutation of similar conserved residues in the Mga-like regulator DmgB from S. dysgalactiae subsp. dysgalactiae showed that CMD-1 and HTH-4 are critical for transcriptional activation in this orthologue, implying that a common mechanism of virulence gene activation may exist for members of the Mga family of regulators.

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Role of mga in growth phase regulation of virulence genes of the group A streptococcus

Cited by 129 publications

References 66 publications

Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activity

Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activity

Multilocus analysis of extracellular putative virulence proteins made by group A Streptococcus: Population genetics, human serologic response, and gene transcription

Domains Required for Transcriptional Activation Show Conservation in the Mga Family of Virulence Gene Regulators

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