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Bacterial Infections

Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System

Artemis Gogos, Michael J. Federle
Andreas J. Bäumler, Editor
Artemis Gogos
aDepartment of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, USA
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Michael J. Federle
bCenter for Biomolecular Sciences, Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
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Andreas J. Bäumler
University of California, Davis
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DOI: 10.1128/IAI.00464-20
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ABSTRACT

Streptococcus pyogenes is a human-restricted pathogen most often found in the human nasopharynx. Multiple bacterial factors are known to contribute to persistent colonization of this niche, and many are important in mucosal immunity and vaccine development. In this work, mice were infected intranasally with transcriptional regulator mutants of the Rgg2/3 quorum sensing (QS) system—a peptide-based signaling system conserved in sequenced isolates of S. pyogenes. Deletion of the QS system’s transcriptional activator (Δrgg2) dramatically diminished the percentage of colonized mice, while deletion of the transcriptional repressor (Δrgg3) increased the percentage of colonized mice compared to that of the wild type (WT). Stimulation of the QS system using synthetic pheromones prior to inoculation did not significantly increase the percentage of animals colonized, indicating that QS-dependent colonization is responsive to the intrinsic conditions within the host upper respiratory tract. Bacterial RNA extracted directly from oropharyngeal swabs and evaluated by quantitative reverse transcription-PCR (qRT-PCR) subsequently confirmed QS upregulation within 1 h of inoculation. In the nasal-associated lymphoid tissue (NALT), a muted inflammatory response to the Δrgg2 bacteria suggests that their rapid elimination failed to elicit the previously characterized response to intranasal inoculation of GAS. This work identifies a new transcriptional regulatory system governing the ability of S. pyogenes to colonize the nasopharynx and provides knowledge that could help lead to decolonization therapeutics.

FOOTNOTES

    • Received 27 July 2020.
    • Accepted 27 July 2020.
    • Accepted manuscript posted online 3 August 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System
Artemis Gogos, Michael J. Federle
Infection and Immunity Sep 2020, 88 (10) e00464-20; DOI: 10.1128/IAI.00464-20

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Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System
Artemis Gogos, Michael J. Federle
Infection and Immunity Sep 2020, 88 (10) e00464-20; DOI: 10.1128/IAI.00464-20
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KEYWORDS

pharyngeal colonization
Pharyngitis
colonization model
innate immune response
host-pathogen interaction
quorum sensing
Streptococcus pyogenes

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