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Environmental pH and peptide signaling control virulence of Streptococcus pyogenes via a quorum-sensing pathway

Author

Listed:
  • Hackwon Do

    (Houston Methodist Research Institute
    Houston Methodist Hospital)

  • Nishanth Makthal

    (Houston Methodist Research Institute
    Houston Methodist Hospital)

  • Arica R. VanderWal

    (Houston Methodist Research Institute
    Houston Methodist Hospital)

  • Matthew Ojeda Saavedra

    (Houston Methodist Research Institute
    Houston Methodist Hospital)

  • Randall J. Olsen

    (Houston Methodist Research Institute
    Houston Methodist Hospital
    Weill Medical College of Cornell University)

  • James M. Musser

    (Houston Methodist Research Institute
    Houston Methodist Hospital
    Weill Medical College of Cornell University)

  • Muthiah Kumaraswami

    (Houston Methodist Research Institute
    Houston Methodist Hospital)

Abstract

Bacteria control gene expression in concert with their population density by a process called quorum sensing, which is modulated by bacterial chemical signals and environmental factors. In the human pathogen Streptococcus pyogenes, production of secreted virulence factor SpeB is controlled by a quorum-sensing pathway and environmental pH. The quorum-sensing pathway consists of a secreted leaderless peptide signal (SIP), and its cognate receptor RopB. Here, we report that the SIP quorum-sensing pathway has a pH-sensing mechanism operative through a pH-sensitive histidine switch located at the base of the SIP-binding pocket of RopB. Environmental acidification induces protonation of His144 and reorganization of hydrogen bonding networks in RopB, which facilitates SIP recognition. The convergence of two disparate signals in the SIP signaling pathway results in induction of SpeB production and increased bacterial virulence. Our findings provide a model for investigating analogous crosstalk in other microorganisms.

Suggested Citation

  • Hackwon Do & Nishanth Makthal & Arica R. VanderWal & Matthew Ojeda Saavedra & Randall J. Olsen & James M. Musser & Muthiah Kumaraswami, 2019. "Environmental pH and peptide signaling control virulence of Streptococcus pyogenes via a quorum-sensing pathway," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10556-8
    DOI: 10.1038/s41467-019-10556-8
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    Cited by:

    1. Shifu Aggarwal & Elaine Huang & Hackwon Do & Nishanth Makthal & Yanyan Li & Eric Bapteste & Philippe Lopez & Charles Bernard & Muthiah Kumaraswami, 2023. "The leaderless communication peptide (LCP) class of quorum-sensing peptides is broadly distributed among Firmicutes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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