ArticleMolecular microbiology2015
Regulatory rewiring confers serotype-specific hyper-virulence in the human pathogen group A Streptococcus.
Article in Molecular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- The group AInfection and immunity · 2025Article
- Clinical Snapshot of Group A Streptococcal Isolates from an Australian Tertiary Hospital.Pathogens (Basel, Switzerland) · 2024Article
- A Case of Necrotizing Fasciitis/Myositis and Streptococcal Toxic Shock Syndrome Caused byInfection and drug resistance · 2024Article
- Hyperphosphorylation of the Group A Streptococcal Control of Virulence Regulator Increases Promoter Occupancy Specifically at Virulence Factor-Encoding Genes.Journal of bacteriology · 2023Article
- Characterization of M-Type-Specific Pilus Expression in Group A Streptococcus.Journal of bacteriology · 2022Article
- General Phenotype of NADase Induction by CLI Treatment inInternational journal of microbiology · 2022Article
- The CovR regulatory network drives the evolution of Group B Streptococcus virulence.PLoS genetics · 2021Article
- The RD2 Pathogenicity Island Modifies the Disease Potential of the Group AInfection and immunity · 2021Article
- Single Amino Acid Replacements in RocA Disrupt Protein-Protein Interactions To Alter the Molecular Pathogenesis of Group AInfection and immunity · 2020Article
- Article
- The group A Streptococcus accessory protein RocA: regulatory activity, interacting partners and influence on disease potential.Molecular microbiology · 2020Article
- In silico characterisation of stand-alone response regulators of Streptococcus pyogenes.PloS one · 2020Article
- Polymorphisms in Regulator of Cov Contribute to the Molecular Pathogenesis of Serotype M28 Group A Streptococcus.The American journal of pathology · 2019Article
- A Mobile Genetic Element Promotes the Association Between Serotype M28 Group A Streptococcus Isolates and Cases of Puerperal Sepsis.The Journal of infectious diseases · 2019Article
- Article
- Gene fitness landscape of group A streptococcus during necrotizing myositis.The Journal of clinical investigation · 2019Article
- Capsular Polysaccharide of Group AMicrobiology spectrum · 2019Article
- RocA Has Serotype-Specific Gene Regulatory and Pathogenesis Activities in Serotype M28 Group A Streptococcus.Infection and immunity · 2018Article
- Phenotypic Variation in the Group AmSphere · 2018Article
- Phosphatase activity of the control of virulence sensor kinase CovS is critical for the pathogenesis of group A streptococcus.PLoS pathogens · 2018Article
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Authors and funding
6 authors.
Funding
Abstract
Phenotypic heterogeneity is commonly observed between isolates of a given pathogen. Epidemiological analyses have identified that some serotypes of the group A Streptococcus (GAS) are non-randomly associated with particular disease manifestations. Here, we present evidence that a contributing factor to the association of serotype M3 GAS isolates with severe invasive infections is the presence of a null mutant allele for the orphan kinase RocA. Through use of RNAseq analysis, we identified that the natural rocA mutation present within M3 isolates leads to the enhanced expression of more than a dozen immunomodulatory virulence factors, enhancing phenotypes such as hemolysis and NAD(+) hydrolysis. Consequently, an M3 GAS isolate survived human phagocytic killing at a level 13-fold higher than a rocA complemented derivative, and was significantly more virulent in a murine bacteremia model of infection. Finally, we identified that RocA functions through the CovR/S two-component system as levels of phosphorylated CovR increase in the presence of functional RocA, and RocA has no regulatory activity following covR or covS mutation. Our data are consistent with RocA interfacing with the CovR/S two-component system, and that the absence of this activity in M3 GAS potentiates the severity of invasive infections caused by isolates of this serotype.
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