biostudies-literatureMuna THNatural Sciences and Engineering Research Council of CanadaNSERCUniversity of ManitobaManitoba Medical Service FoundationCanadian Foundation for Innovationgkae1200https://www.ebi.ac.uk/biostudies/studies/S-EPMC11754733biostudies-literatureUnknown53(2)Streptococcus pyogenes, or Group A Streptococcus (GAS), is a commensal bacteria and human pathogen. Central to GAS pathogenesis is the presence of prophage encoded virulence genes. The conserved phage gene for the protein paratox (Prx) is genetically linked to virulence genes, but the reason for this linkage is unknown. Prx inhibits GAS quorum sensing and natural competence by binding the transcription factor ComR. However, inhibiting ComR does not explain the virulence gene linkage. To address this, we took a mass spectrometry approach to search for other Prx interaction partners. The data demonstrates that Prx binds numerous DNA-binding proteins and transcriptional regulators. We show binding of Prx in vitro with the GAS protein Esub1 (SpyM3_0890) and the phage protein JM3 (SpyM3_1246). Nucleic acids researchThe phage protein paratox is a multifunctional metabolic regulator of Streptococcus.PMC11754733RGPIN-2018-04968RGPIN-2022-05015378418-2020-10Krokhin OVPrehna GMuna THHorne JRutbeek NRLao YWfalseThe phage protein paratox is a multifunctional metabolic regulator of Streptococcus.Streptococcus pyogenes, or Group A Streptococcus (GAS), is a commensal bacteria and human pathogen. Central to GAS pathogenesis is the presence of prophage encoded virulence genes. The conserved phage gene for the protein paratox (Prx) is genetically linked to virulence genes, but the reason for this linkage is unknown. Prx inhibits GAS quorum sensing and natural competence by binding the transcription factor ComR. However, inhibiting ComR does not explain the virulence gene linkage. To address this, we took a mass spectrometry approach to search for other Prx interaction partners. The data demonstrates that Prx binds numerous DNA-binding proteins and transcriptional regulators. We show binding of Prx in vitro with the GAS protein Esub1 (SpyM3_0890) and the phage protein JM3 (SpyM3_1246). 2025-01-01T00:00:00Z2025 Jan2026-06-01T10:29:45.295Z2025-04-05T10:18:22.74ZS-EPMC117547333967379810.1093/nar/gkae1200