Trial reportThe Journal of biological chemistry2013
Complement-mediated opsonization of invasive group A Streptococcus pyogenes strain AP53 is regulated by the bacterial two-component cluster of virulence responder/sensor (CovRS) system.
Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Group aMicrobiology spectrum · 2025Article
- Conservation of C4BP-binding sequence patterns in Streptococcus pyogenes M and Enn proteins.The Journal of biological chemistry · 2024Article
- Binding of the kringle-2 domain of human plasminogen to streptococcal PAM-type M-protein causes dissociation of PAM dimers.MicrobiologyOpen · 2021Article
- Group AFrontiers in cardiovascular medicine · 2021Article
- Host Pathways of Hemostasis that Regulate Group A Streptococcus pyogenes Pathogenicity.Current drug targets · 2020Article
- Solution structural model of the complex of the binding regions of human plasminogen with its M-protein receptor from Streptococcus pyogenes.Journal of structural biology · 2019Article
- Contributions of different modules of the plasminogen-binding Streptococcus pyogenes M-protein that mediate its functional dimerization.Journal of structural biology · 2018Article
- Incremental Contributions of FbaA and Other Impetigo-Associated Surface Proteins to Fitness and Virulence of a Classical Group A Streptococcal Skin Strain.Infection and immunity · 2017Article
- Conformationally organized lysine isosteres inThe Journal of biological chemistry · 2017Article
- Variable region in streptococcal M-proteins provides stable binding with host fibrinogen for plasminogen-mediated bacterial invasion.The Journal of biological chemistry · 2017Article
- The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes.Infection and immunity · 2017Article
- CovR Regulates Streptococcus mutans Susceptibility To Complement Immunity and Survival in Blood.Infection and immunity · 2016Article
- Streptococcus pyogenes Employs Strain-dependent Mechanisms of C3b Inactivation to Inhibit Phagocytosis and Killing of Bacteria.The Journal of biological chemistry · 2016Article
- Necrotizing Fasciitis in Paroxysmal Nocturnal Hemoglobinuria.Case reports in hematology · 2015Article
- Unique genomic arrangements in an invasive serotype M23 strain of Streptococcus pyogenes identify genes that induce hypervirulence.Journal of bacteriology · 2014Article
- Dimerization is not a determining factor for functional high affinity human plasminogen binding by the group A streptococcal virulence factor PAM and is mediated by specific residues within the PAM a1a2 domain.The Journal of biological chemistry · 2014Article
- Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Group A Streptococcus pyogenes (GAS) strain AP53 is a primary isolate from a patient with necrotizing fasciitis. These AP53 cells contain an inactivating mutation in the sensor component of the cluster of virulence (cov) responder (R)/sensor (S) two-component gene regulatory system (covRS), which enhances the virulence of the primary strain, AP53/covR(+)S(-). However, specific mechanisms by which the covRS system regulates the survival of GAS in humans are incomplete. Here, we show a key role for covRS in the regulation of opsonophagocytosis of AP53 by human neutrophils. AP53/covR(+)S(-) cells displayed potent binding of host complement inhibitors of C3 convertase, viz. Factor H (FH) and C4-binding protein (C4BP), which concomitantly led to minimal C3b deposition on AP53 cells, further showing that these plasma protein inhibitors are active on GAS cells. This resulted in weak killing of the bacteria by human neutrophils and a corresponding high death rate of mice after injection of these cells. After targeted allelic alteration of covS(-) to wild-type covS (covS(+)), a dramatic loss of FH and C4BP binding to the AP53/covR(+)S(+) cells was observed. This resulted in elevated C3b deposition on AP53/covR(+)S(+) cells, a high level of opsonophagocytosis by human neutrophils, and a very low death rate of mice infected with AP53/covR(+)S(+). We show that covRS is a critical transcriptional regulator of genes directing AP53 killing by neutrophils and regulates the levels of the receptors for FH and C4BP, which we identify as the products of the fba and enn genes, respectively.
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Registered trials
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