Title: | Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System |
Address: | "Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, USA. Center for Biomolecular Sciences, Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA mfederle@uic.edu" |
ISSN/ISBN: | 1098-5522 (Electronic) 0019-9567 (Print) 0019-9567 (Linking) |
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 (Deltargg2) dramatically diminished the percentage of colonized mice, while deletion of the transcriptional repressor (Deltargg3) 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 Deltargg2 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" |
Keywords: | "Animals Bacterial Proteins/genetics/*metabolism Disease Models, Animal Gene Expression Regulation, Bacterial Mice Mutation Oropharynx/*microbiology Pharyngitis/microbiology *Quorum Sensing/genetics Streptococcal Infections/*microbiology Streptococcus pyog;" |
Notes: | "MedlineGogos, Artemis Federle, Michael J eng F30 AI136359/AI/NIAID NIH HHS/ R01 AI091779/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2020/08/05 Infect Immun. 2020 Sep 18; 88(10):e00464-20. doi: 10.1128/IAI.00464-20. Print 2020 Sep 18" |