ArticleInfection and immunity2008
CcpA-mediated repression of streptolysin S expression and virulence in the group A streptococcus.
Article in Infection and immunity, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 79 citations in OpenAlex.
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- Streptolysin S is required for Streptococcus pyogenes nasopharyngeal and skin infection in HLA-transgenic mice.PLoS pathogens · 2024Article
- Elucidation of independently modulated genes inmSystems · 2023Article
- Central carbon flux controls growth/damage balance for Streptococcus pyogenes.PLoS pathogens · 2023Article
- Studies of Streptococcus anginosus Virulence in Dictyostelium discoideum and Galleria mellonella Models.Infection and immunity · 2023Article
- Genome-wide analysis of in vivo CcpA binding with and without its key co-factor HPr in the major human pathogen group A Streptococcus.Molecular microbiology · 2021Article
- Phosphotransferase System Uptake and Metabolism of the β-Glucoside Salicin Impact Group A Streptococcal Bloodstream Survival and Soft Tissue Infection.Infection and immunity · 2020Article
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- Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis.Applied and environmental microbiology · 2019Article
- Hydrogen Peroxide Production of Group A Streptococci (GAS) is emm-Type Dependent and Increased at Low Temperatures.Current microbiology · 2019Article
- Transcriptome, Phenotypic, and Virulence Analysis ofFrontiers in cellular and infection microbiology · 2019Article
- β-HemolyticJournal of oral microbiology · 2019Article
- CcpA Coordinates Growth/Damage Balance for Streptococcus pyogenes Pathogenesis.Scientific reports · 2018Article
- Regulation of the β-hemolysin gene cluster of Streptococcus anginosus by CcpA.Scientific reports · 2018Article
- Glucose Levels Alter the Mga Virulence Regulon in the Group A Streptococcus.Scientific reports · 2018Article
- The Roles of Two Type VI Secretion Systems inFrontiers in microbiology · 2018Article
- Route of Glucose Uptake in the Group a Streptococcus Impacts SLS-Mediated Hemolysis and Survival in Human Blood.Frontiers in cellular and infection microbiology · 2018Article
- A PTS EII mutant library in Group A Streptococcus identifies a promiscuous man-family PTS transporter influencing SLS-mediated hemolysis.Molecular microbiology · 2017Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
CcpA is the global mediator of carbon catabolite repression (CCR) in gram-positive bacteria, and growing evidence from several pathogens, including the group A streptococcus (GAS), suggests that CcpA plays an important role in virulence gene regulation. In this study, a deletion of ccpA in an invasive M1 GAS strain was used to test the contribution of CcpA to pathogenesis in mice. Surprisingly, the DeltaccpA mutant exhibited a dramatic "hypervirulent" phenotype compared to the parental MGAS5005 strain, reflected as increased lethality in a model of systemic infection (intraperitoneal administration) and larger lesion size in a model of skin infection (subcutaneous administration). Expression of ccpA in trans from its native promoter was able to complement both phenotypes, suggesting that CcpA acts to repress virulence in GAS. To identify the CcpA-regulated gene(s) involved, a transcriptome analysis was performed on mid-logarithmic-phase cells grown in rich medium. CcpA was found to primarily repress 6% of the GAS genome (124 genes), including genes involved in sugar metabolism, transcriptional regulation, and virulence. Notably, the entire sag operon necessary for streptolysin S (SLS) production was under CcpA-mediated CCR, as was SLS hemolytic activity. Purified CcpA-His bound specifically to a cre within sagAp, demonstrating direct repression of the operon. Finally, SLS activity is required for the increased virulence of a DeltaccpA mutant during systemic infection but did not affect virulence in a wild-type background. Thus, CcpA acts to repress SLS activity and virulence during systemic infection in mice, revealing an important link between carbon metabolism and GAS pathogenesis.
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