ArticleJournal of bacteriology2015
CovRS-Regulated Transcriptome Analysis of a Hypervirulent M23 Strain of Group A Streptococcus pyogenes Provides New Insights into Virulence Determinants.
Article in Journal of bacteriology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- A Novel Translational Reprogramming of the Insertion Sequence IS1239 by 1-bp Deletion Resulted in Polymorphism of C-Terminal Amino Acid Sequences in the Pathogenic BacteriumJournal of microbiology and biotechnology · 2026Article
- Group aMicrobiology spectrum · 2025Article
- The invasive GAS puzzle in Italy: genomic insights from a hospital cohort in a fragmented surveillance landscape.Frontiers in cellular and infection microbiology · 2025Article
- Single Amino Acid Replacements in RocA Disrupt Protein-Protein Interactions To Alter the Molecular Pathogenesis of Group AInfection and immunity · 2020Article
- The M Protein of Streptococcus pyogenes Strain AP53 Retains Cell Surface Functional Plasminogen Binding after Inactivation of the Sortase A Gene.Journal of bacteriology · 2020Article
- Article
- Host Pathways of Hemostasis that Regulate Group A Streptococcus pyogenes Pathogenicity.Current drug targets · 2020Article
- Polymorphisms in Regulator of Cov Contribute to the Molecular Pathogenesis of Serotype M28 Group A Streptococcus.The American journal of pathology · 2019Article
- Article
- Use of a Phosphorylation Site Mutant To Identify Distinct Modes of Gene Repression by the Control of Virulence Regulator (CovR) in Streptococcus pyogenes.Journal of bacteriology · 2017Article
- Evolutionary Constraints Shaping Streptococcus pyogenes-Host Interactions.Trends in microbiology · 2017Review
- Immunization with a streptococcal multiple-epitope recombinant protein protects mice against invasive group A streptococcal infection.PloS one · 2017Article
- Null Mutations of Group A Streptococcus Orphan Kinase RocA: Selection in Mouse Infection and Comparison with CovS Mutations in Alteration of In Vitro and In Vivo Protease SpeB Expression and Virulence.Infection and immunity · 2017Article
- Novel genomic rearrangements mediated by multiple genetic elements in Streptococcus pyogenes M23ND confer potential for evolutionary persistence.Microbiology (Reading, England) · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledThe two-component control of virulence (Cov) regulator (R)-sensor (S) (CovRS) regulates the virulence of Streptococcus pyogenes (group A Streptococcus [GAS]). Inactivation of CovS during infection switches the pathogenicity of GAS to a more invasive form by regulating transcription of diverse virulence genes via CovR. However, the manner in which CovRS controls virulence through expression of extended gene families has not been fully determined. In the current study, the CovS-regulated gene expression profiles of a hypervirulent emm23 GAS strain (M23ND/CovS negative [M23ND/CovS(-)]) and a noninvasive isogenic strain (M23ND/CovS(+)), under different growth conditions, were investigated. RNA sequencing identified altered expression of ∼ 349 genes (18% of the chromosome). The data demonstrated that M23ND/CovS(-) achieved hypervirulence by allowing enhanced expression of genes responsible for antiphagocytosis (e.g., hasABC), by abrogating expression of toxin genes (e.g., speB), and by compromising gene products with dispensable functions (e.g., sfb1). Among these genes, several (e.g., parE and parC) were not previously reported to be regulated by CovRS. Furthermore, the study revealed that CovS also modulated the expression of a broad spectrum of metabolic genes that maximized nutrient utilization and energy metabolism during growth and dissemination, where the bacteria encounter large variations in available nutrients, thus restructuring metabolism of GAS for adaption to diverse growth environments. From constructing a genome-scale metabolic model, we identified 16 nonredundant metabolic gene modules that constitute unique nutrient sources. These genes were proposed to be essential for pathogen growth and are likely associated with GAS virulence. The genome-wide prediction of genes associated with virulence identifies new candidate genes that potentially contribute to GAS virulence. IMPORTANCE: The CovRS system modulates transcription of ∼ 18% of the genes in the Streptococcus pyogenes genome. Mutations that inactivate CovR or CovS enhance the virulence of this bacterium. We determined complete transcriptomes of a naturally CovS-inactivated invasive deep tissue isolate of an emm23 strain of S. pyogenes (M23ND) and its complemented avirulent variant (CovS(+)). We identified diverse virulence genes whose altered expression revealed a genetic switching of a nonvirulent form of M23ND to a highly virulent strain. Furthermore, we also systematically uncovered for the first time the comparative levels of expression of a broad spectrum of metabolic genes, which reflected different metabolic needs of the bacterium as it invaded deeper tissue of the human host.
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