ArticlePloS one2014
Mutations in the control of virulence sensor gene from Streptococcus pyogenes after infection in mice lead to clonal bacterial variants with altered gene regulatory activity and virulence.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Group aMicrobiology spectrum · 2025Article
- Rapid expansion and international spread of M1Nature communications · 2024Article
- Group A Streptococcus strains causing meningitis without distinct invasive phenotype.MicrobiologyOpen · 2024Article
- Elucidation of independently modulated genes inmSystems · 2023Article
- Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis.Applied and environmental microbiology · 2019Article
- Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis.Nature genetics · 2019Article
- ModelingFrontiers in cellular and infection microbiology · 2019Review
- Article
- Evolutionary Constraints Shaping Streptococcus pyogenes-Host Interactions.Trends in microbiology · 2017Review
- The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes.Infection and immunity · 2017Article
- Regulatory gene mutation: a driving force behind group a Streptococcus strain- and serotype-specific variation.Molecular microbiology · 2017Review
- Genomic Landscape of Intrahost Variation in Group A Streptococcus: Repeated and Abundant Mutational Inactivation of the fabT Gene Encoding a Regulator of Fatty Acid Synthesis.Infection and immunity · 2016Article
- Genomic Characterization of a Pattern D Streptococcus pyogenes emm53 Isolate Reveals a Genetic Rationale for Invasive Skin Tropicity.Journal of bacteriology · 2016Article
- Activation of band 3 mediates group A Streptococcus streptolysin S-based beta-haemolysis.Nature microbiology · 2016Article
- CovRS-Regulated Transcriptome Analysis of a Hypervirulent M23 Strain of Group A Streptococcus pyogenes Provides New Insights into Virulence Determinants.Journal of bacteriology · 2015Article
- Direct Host Plasminogen Binding to Bacterial Surface M-protein in Pattern D Strains of Streptococcus pyogenes Is Required for Activation by Its Natural Coinherited SK2b Protein.The Journal of biological chemistry · 2015Article
- Consequences of the variability of the CovRS and RopB regulators among Streptococcus pyogenes causing human infections.Scientific reports · 2015Article
- covR Mediated Antibiofilm Activity of 3-Furancarboxaldehyde Increases the Virulence of Group A Streptococcus.PloS one · 2015Article
- Unique genomic arrangements in an invasive serotype M23 strain of Streptococcus pyogenes identify genes that induce hypervirulence.Journal of bacteriology · 2014Article
- Comparative Genome Analyses ofmSystemsArticle
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7 authors.
Funding
Abstract
The cluster of virulence sensor (CovS)/responder (CovR) two-component operon (CovRS) regulates ∼15% of the genes of the Group A Streptococcal pyogenes (GAS) genome. Bacterial clones containing inactivating mutations in the covS gene have been isolated from patients with virulent invasive diseases. We report herein an assessment of the nature and types of covS mutations that can occur in both virulent and nonvirulent GAS strains, and assess whether a nonvirulent GAS can attain enhanced virulence through this mechanism. A group of mice were infected with a globally-disseminated clonal M1T1 GAS (isolate 5448), containing wild-type (WT) CovRS (5448/CovR+S+), or less virulent engineered GAS strains, AP53/CovR+S+ and Manfredo M5/CovR+S+. SpeB negative GAS clones from wound sites and/or from bacteria disseminated to the spleen were isolated and the covS gene was subjected to DNA sequence analysis. Numerous examples of inactivating mutations were found in CovS in all regions of the gene. The mutations found included frame-shift insertions and deletions, and in-frame small and large deletions in the gene. Many of the mutations found resulted in early translation termination of CovS. Thus, the covS gene is a genomic mutagenic target that gives GAS enhanced virulence. In cases wherein CovS- was discovered, these clonal variants exhibited high lethality, further suggesting that randomly mutated covS genes occur during the course of infection, and lead to the development of a more invasive infection.
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