ArticlePLoS pathogens2013
RocA truncation underpins hyper-encapsulation, carriage longevity and transmissibility of serotype M18 group A streptococci.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 67 citations in OpenAlex.
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- Characterization of the RofA regulon in the pandemic M1Microbial genomics · 2023Article
- Structure-activity studies of Streptococcus pyogenes enzyme SpyCEP reveal high affinity for CXCL8 in the SpyCEP C-terminal.Scientific reports · 2023Article
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- The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance.PLoS pathogens · 2022Article
- TheJournal of bacteriology · 2021Article
- Single Amino Acid Replacements in RocA Disrupt Protein-Protein Interactions To Alter the Molecular Pathogenesis of Group AInfection and immunity · 2020Article
- Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection.Nature communications · 2020Article
- Article
- The group A Streptococcus accessory protein RocA: regulatory activity, interacting partners and influence on disease potential.Molecular microbiology · 2020Article
- Article
- 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
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7 authors at 3 institutions in 1 country.
Funding
Abstract
Group A streptococcal isolates of serotype M18 are historically associated with epidemic waves of pharyngitis and the non-suppurative immune sequela rheumatic fever. The serotype is defined by a unique, highly encapsulated phenotype, yet the molecular basis for this unusual colony morphology is unknown. Here we identify a truncation in the regulatory protein RocA, unique to and conserved within our serotype M18 GAS collection, and demonstrate that it underlies the characteristic M18 capsule phenotype. Reciprocal allelic exchange mutagenesis of rocA between M18 GAS and M89 GAS demonstrated that truncation of RocA was both necessary and sufficient for hyper-encapsulation via up-regulation of both precursors required for hyaluronic acid synthesis. Although RocA was shown to positively enhance covR transcription, quantitative proteomics revealed RocA to be a metabolic regulator with activity beyond the CovR/S regulon. M18 GAS demonstrated a uniquely protuberant chain formation following culture on agar that was dependent on excess capsule and the RocA mutation. Correction of the M18 rocA mutation reduced GAS survival in human blood, and in vivo naso-pharyngeal carriage longevity in a murine model, with an associated drop in bacterial airborne transmission during infection. In summary, a naturally occurring truncation in a regulator explains the encapsulation phenotype, carriage longevity and transmissibility of M18 GAS, highlighting the close interrelation of metabolism, capsule and virulence.
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