Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox

dc.contributor.authorRutbeek, Nicole R.
dc.contributor.authorRezasoltani, Hanieh
dc.contributor.authorPatel, Trushar R.
dc.contributor.authorKhajehpour, Mazdak
dc.contributor.authorPrehna, Gerd
dc.date.accessioned2022-10-28T19:18:49Z
dc.date.available2022-10-28T19:18:49Z
dc.date.issued2021
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesen_US
dc.description.abstractStreptococcus pyogenes, or Group A Streptococcus, is a Gram-positive bacterium that can be both a human commensal and a pathogen. Central to this dichotomy are temperate bacteriophages that incorporate into the bacterial genome as prophages. These genetic elements encode both the phage proteins and the toxins harmful to the human host. One such conserved phage protein, paratox (Prx), is always found encoded adjacent to the toxin genes, and this linkage is preserved during all stages of the phage life cycle. Within S. pyogenes, Prx functions to inhibit the quorum-sensing receptor-signal pair ComRS, the master regulator of natural competence, or the ability to uptake endogenous DNA. However, the mechanism by which Prx directly binds and inhibits the receptor ComR is unknown. To understand how Prx inhibits ComR at the molecular level, we pursued an X-ray crystal structure of Prx bound to ComR. The structural data supported by solution X-ray scattering data demonstrate that Prx induces a conformational change in ComR to directly access its DNA-binding domain. Furthermore, electromobility shift assays and competition binding assays reveal that Prx effectively uncouples the interdomain conformational change required for activation of ComR via the signaling molecule XIP. Although to our knowledge the molecular mechanism of quorum-sensing inhibition by Prx is unique, it is analogous to the mechanism employed by the phage protein Aqs1 in Pseudomonas aeruginosa. Together, this demonstrates an example of convergent evolution between Gram-positive and Gram-negative phages to inhibit quorum-sensing and highlights the versatility of small phage proteins.en_US
dc.identifier.citationRutbeek, N. R., Rezasoltani, H., Patel, T. R., Khajehpour M., & Prehna, G. (2021). Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox. Journal of Biological Chemistry, 297(3), Article 100992. Conclusion: Significantly greater improvement in addictive symptoms and recovery capital of couple adjustment, mental health, and life stress was found in the working vs not-working group. Compared to individual-based TAU, exploratory findings indicate that the systemic treatment of CCT showed a clearer and more consistent difference in improved working days, addictive symptoms and recovery capital. Replication with larger samples is needed to generalize these results.en_US
dc.identifier.urihttps://hdl.handle.net/10133/6368
dc.language.isoen_CAen_US
dc.publisherElsevieren_US
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.faculty
dc.publisher.institutionUniversity of Manitoba
dc.publisher.institutionUniversity of Lethbridge
dc.subjectParatoxen_US
dc.subjectPrxen_US
dc.subjectBacteriophageen_US
dc.subjectNatural competenceen_US
dc.subjectComRSen_US
dc.subjectXIPen_US
dc.subjectQuorum sensingen_US
dc.subjectSolution X-ray scatteringen_US
dc.subject.lcshStreptococcus
dc.subject.lcshStreptococcus pyogenes
dc.subject.lcshBacteriophages
dc.subject.lcshX-ray crystallography
dc.subject.lcshX-rays--Scattering
dc.titleMolecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratoxen_US
dc.typeArticleen_US
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