Unraveling the Regulatory Network in
            <i>Streptococcus pyogenes</i>
            : the Global Response Regulator CovR Represses
            <i>rivR</i>
            Directly

Roberts, Samantha; Churchward, Gordon; Scott, June R.

doi:10.1128/jb.01026-06

Cited by 30 publications

(44 citation statements)

References 19 publications

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“…CovR is a very important response regulator in many pathogenic streptococci; in group A streptococci (GAS), CovR generally acts as a repressor by directly binding to the promoter region of various genes (4,11,16). However, CovR repression at some promoters is indirect and mediated by other transcriptional regulators, such as RivR (38). CovR also acts as a transcriptional activator via direct interaction with the promoters, although direct activation by CovR has been demonstrated only for the dppA promoter of GAS (14).…”

Section: Vol 189 2007 Gbpc Expression In S Mutans 6527mentioning

confidence: 99%

Regulation of gbpC Expression in Streptococcus mutans

2007

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Streptococcus mutans, the principal causative agent of dental caries, produces four glucan-binding proteins (Gbp) that play major roles in bacterial adherence and pathogenesis. One of these proteins, GbpC, is an important cell surface protein involved in biofilm formation. GbpC is also important for cariogenesis, bacteremia, and infective endocarditis. In this study, we examined the regulation of gbpC expression in S. mutans strain UA159. We found that gbpC expression attains the maximum level at mid-exponential growth phase, and the half-life of the transcript is less than 2 min. Expression from PgbpC was measured using a PgbpC-gusA transcriptional fusion reporter and was analyzed under various stress conditions, including thermal, osmotic, and acid stresses. Expression of gbpC is induced under conditions of thermal stress but is repressed during growth at low pH, whereas osmotic stress had no effect on expression from PgbpC. The results from the expression analyses were further confirmed using semiquantitative reverse transcription-PCR analysis. Our results also reveal that CovR, a global response regulator in many Streptococcus spp., represses gbpC expression at the transcriptional level. We demonstrated that purified CovR protein binds directly to the promoter region of PgbpC to repress gbpC expression. Using a DNase I protection assay, we showed that CovR binds to DNA sequences surrounding PgbpC from bases ؊68 to 28 (where base 1 is the start of transcription). In summary, our results indicate that various stress conditions modulate the expression of gbpC and that CovR negatively regulates the expression of the gbpC gene by directly binding to the promoter region.

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Section: Vol 189 2007 Gbpc Expression In S Mutans 6527mentioning

confidence: 99%

Regulation of gbpC Expression in Streptococcus mutans

2007

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“…CovRS controls expression of about 15% of the GAS genome either directly or indirectly (21). Unlike the DNA binding protein (response regulator) of most TCS, the response regulator CovR represses most of the genes it controls (18,20,35,48). It also represses its own transcription (23).…”

Section: Importance Of Covrs In Pathogenesismentioning

confidence: 99%

Streptococcus pyogenesCovRS Mediates Growth in Iron Starvation and in the Presence of the Human Cationic Antimicrobial Peptide LL-37

2009

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“…RivR (RofA-like protein IV) is a member of the RofA-like family of regulatory proteins that are conserved across streptococcal species (31,32). The rivR gene is located upstream of a putative sRNA-encoding gene, rivX.…”

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confidence: 99%

Natural Disruption of Two Regulatory Networks in Serotype M3 Group A Streptococcus Isolates Contributes to the Virulence Factor Profile of This Hypervirulent Serotype

et al. 2014

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c Despite the public health challenges associated with the emergence of new pathogenic bacterial strains and/or serotypes, there is a dearth of information regarding the molecular mechanisms that drive this variation. Here, we began to address the mechanisms behind serotype-specific variation between serotype M1 and M3 strains of the human pathogen Streptococcus pyogenes (the group A Streptococcus [GAS]). Spatially diverse contemporary clinical serotype M3 isolates were discovered to contain identical inactivating mutations within genes encoding two regulatory systems that control the expression of important virulence factors, including the thrombolytic agent streptokinase, the protease inhibitor-binding protein-G-related ␣ 2 -macroglobulinbinding (GRAB) protein, and the antiphagocytic hyaluronic acid capsule. Subsequent analysis of a larger collection of isolates determined that M3 GAS, since at least the 1920s, has harbored a 4-bp deletion in the fasC gene of the fasBCAX regulatory system and an inactivating polymorphism in the rivR regulator-encoding gene. The fasC and rivR mutations in M3 isolates directly affect the virulence factor profile of M3 GAS, as evident by a reduction in streptokinase expression and an enhancement of GRAB expression. Complementation of the fasC mutation in M3 GAS significantly enhanced levels of the small regulatory RNA FasX, which in turn enhanced streptokinase expression. Complementation of the rivR mutation in M3 GAS restored the regulation of grab mRNA abundance but did not alter capsule mRNA levels. While important, the fasC and rivR mutations do not provide a full explanation for why serotype M3 strains are associated with unusually severe invasive infections; thus, further investigation is warranted.

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Unraveling the Regulatory Network in Streptococcus pyogenes : the Global Response Regulator CovR Represses rivR Directly

Cited by 30 publications

References 19 publications

Regulation of gbpC Expression in Streptococcus mutans

Regulation of gbpC Expression in Streptococcus mutans

Streptococcus pyogenesCovRS Mediates Growth in Iron Starvation and in the Presence of the Human Cationic Antimicrobial Peptide LL-37

Natural Disruption of Two Regulatory Networks in Serotype M3 Group A Streptococcus Isolates Contributes to the Virulence Factor Profile of This Hypervirulent Serotype

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