Carbon Catabolite Repression on the Rgg2/3 Quorum Sensing System in Streptococcus pyogenes is Mediated by PTS Man and Mga

2021 ◽  
Author(s):  
Jerry K. K. Woo ◽  
Kevin S. McIver ◽  
Michael J. Federle
Keyword(s):  
Quorum Sensing ◽  
Streptococcus Pyogenes ◽  
Catabolite Repression ◽  
Carbon Catabolite Repression ◽  
Sensing System ◽  
Quorum Sensing System

#99: Streptococcus pyogenes Utilizes the Peptide-Based Rgg 2/3 Quorum Sensing System During Oropharyngeal Colonization

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S10-S10
Author(s):  
Artemis Gogos ◽  
Michael J Federle
Keyword(s):  
Quorum Sensing ◽  
Streptococcus Pyogenes ◽  
Lymphoid Tissue ◽  
Transcriptional Activator ◽  
Rt Pcr ◽  
Sensing System ◽  
Bacterial Rna ◽  
Quorum Sensing System ◽  
Luciferase Reporters

Abstract Background Streptococcus pyogenes is a human-restricted pathogen most often found in the human nasopharynx. Multiple bacterial factors have been found to contribute to persistent colonization of this niche, and many of these factors are important in mucosal immunity and vaccine development. In this work, we infected mice intranasally with transcriptional regulator mutants of the Rgg2/3 quorum sensing (QS) system—a peptide-based signaling system conserved in all sequenced isolates of S. pyogenes. Methods Three-week-old CD1 mice were intranasally infected with ~107 CFU of S. pyogenes strain MGAS315. Calcium alginate throat swabs were used to monitor nasopharyngeal colonization by the bacteria over time. Luciferase reporters used alongside an IVIS camera were able to show quorum sensing activity levels after inoculation into the mouse nose. Bacterial RNA was isolated from the throat of the mice and quantitative RT–PCR was performed on the samples to corroborate the luciferase reporter data. The nasal-associated lymphoid tissue (NALT) was excised and its supernatants were subjected to 32-plex murine cytokine and chemokine analysis (Millipore). Results Deletion of the QS system’s transcriptional activator (Δrgg2) dramatically diminished the percentage of colonized mice. Deletion of the transcriptional repressor (Δrgg3) increased the percentage of colonized mice compared with wild type. Stimulation of the QS system using synthetic pheromones prior to inoculation did not significantly increase the percentage of animals colonized, indicating that activity of the QS system is responsive to conditions of the host nasopharynx. Mice inoculated with QS-dependent luciferase reporters were subjected to in vivo imaging and showed activation within 1 hour. Bacterial RNA extracted directly from oropharyngeal swabs and evaluated by quantitative RT–PCR subsequently confirmed QS upregulation within 1 hour of inoculation. In the nasal-associated lymphoid tissue (NALT), a muted inflammatory response to the Δrgg2 bacteria suggests that their rapid elimination fails to elicit the previously characterized response to intranasal inoculation of GAS. Conclusions Deletion of the Rgg2 transcriptional activator of the Rgg 2/3 quorum sensing system eliminates colonization of the murine nasopharynx and changes the transcriptional profile of the bacteria in this niche. An existing small-molecule inhibitor of the Rgg2/3 system was unable to inhibit QS activation in vivo, likely due to the suboptimal achievable doses; however, results of our study indicate inhibition of QS may diminish the oropharyngeal colonization of S. pyogenes and argue for further development.

scholarly journals Colonization of the murine oropharynx by Streptococcus pyogenes is governed by the Rgg2/3 quorum sensing system

2020 ◽  
Author(s):  
Artemis Gogos ◽  
Michael J. Federle
Keyword(s):  
Quorum Sensing ◽  
Streptococcus Pyogenes ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Regulatory System ◽  
Transcriptional Activator ◽  
Upper Respiratory Tract ◽  
Sensing System ◽  
Molecular Therapeutics ◽  
Quorum Sensing System

AbstractStreptococcus 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 wild type. 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 RT-PCR subsequently confirmed QS upregulation within one hour 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.Author SummaryStreptococcus pyogenes is responsible for a wide spectrum of diseases ranging from common pharyngitis to infrequent invasive infections like necrotizing fasciitis. The ability of this microorganism to persist in the human oropharynx predisposes colonized individuals to a variety of superficial and invasive diseases which lead to significant morbidities and mortality. Identification of the regulatory systems that augment the bacteria’s ability to colonize the oropharynx provides potential targets against which molecular therapeutics can be designed. Here we show that the Rgg2/3 quorum sensing system, an interbacterial communication system, governs the ability of S. pyogenes to colonize the murine oropharynx. Disruption of the system’s transcriptional activator reduced colonization dramatically, eliminated the transcription of two sets of genes known to be activated by the Rgg2/3 system, and tempered the innate immune response seen when S. pyogenes is intranasally infected into the mouse.

scholarly journals Complete Genome Sequence of Streptococcus pyogenesemm14 JS95, a Necrotizing Fasciitis Strain Isolated in Israel

2017 ◽  
Vol 5 (11) ◽  
Author(s):  
Jacqueline L. Y. Chee ◽  
Miriam Ravins ◽  
Emanuel Hanski ◽  
Swaine L. Chen
Keyword(s):  
Quorum Sensing ◽  
Necrotizing Fasciitis ◽  
Genome Sequence ◽  
Streptococcus Pyogenes ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Content Type ◽  
Sensing System ◽  
Quorum Sensing System

ABSTRACT Here, we report the complete genome sequence of the Streptococcus pyogenes emm14 strain JS95, isolated from a patient with necrotizing fasciitis. The streptococcal invasion locus (sil), the first quorum-sensing system characterized in S. pyogenes, was identified in this strain.

scholarly journals Non-Native Peptides Capable of Pan-Activating the agr Quorum Sensing System across Multiple Specificity Groups of Staphylococcus epidermidis

2021 ◽  
Author(s):  
Korbin H. J. West ◽  
Wenqi Shen ◽  
Emma L. Eisenbraun ◽  
Tian Yang ◽  
Joseph K. Vasquez ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Staphylococcus Epidermidis ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Native Peptides

Investigating the Quorum Sensing System in Halophilic Bacteria

2015 ◽  
pp. 189-207 ◽  
Author(s):  
Tommonaro Giuseppina ◽  
Abbamondi Gennaro Roberto ◽  
Toksoy Oner Ebru ◽  
Nicolaus Barbara
Keyword(s):  
Quorum Sensing ◽  
Halophilic Bacteria ◽  
Sensing System ◽  
Quorum Sensing System

scholarly journals Inhibition of exoprotease production in Aeromonas hydrophila by rhizome extract of temu lawak (Curcuma xanthorrhiza (Roxb.)

2006 ◽  
Vol 4 (2) ◽  
pp. 45-54
Author(s):  
UMI LESTARI ◽  
ARTINI PANGASTUTI ◽  
ARI SUSILOWATI
Keyword(s):  
Quorum Sensing ◽  
Ethyl Acetate ◽  
Aeromonas Hydrophila ◽  
Ethanol Extract ◽  
Homoserine Lactone ◽  
Sensing System ◽  
Development Of Resistance ◽  
Quorum Sensing System ◽  
Assay Result ◽  
Curcuma Xanthorrhiza

Conventional treatment of infectious diseases is based on compounds that kill or inhibit the growth of bacteria. A major concern with this approach is the frequent development of resistance to antimicrobial compounds. The discovery of communication (quorum sensing system) regulating bacterial virulence opens up ways to control certain bacterial infectious without interfering the growth. The fish pathogen Aeromonas hydrophila produces quorum sensing signal, NButanoyl-L-Homoserine Lactone (C4-HSL). C4-HSL regulates exoprotease synthesis, a virulence factor of A. hydrophila. Expression of exoprotease can be blocked by using quorum sensing inhibitor. The purpose of this study was to investigate the inhibiting effect of Curcuma xanthorrhiza (Roxb.) extract to exoprotease production of A. hydrophila. Extraction was conducted by using n-hexane, ethyl acetate and ethanol. The qualitative exoprotease assay result showed that n-hexane extract of C. xanthorrhiza had not effect on growth and exoprotease production of A. hydrophila. Meanwhile, 4% of ethyl acetate and ethanol extract of C. xanthorrhiza can inhibit exoprotease production without affecting A. hydrophilla growth. The quantitative exoprotease assay result showed that 4% of ethyl acetate and ethanol extract can inhibit the exoprotease production by 93,9% and 95,6%. The growth of A. hydrophila was not affected by this extract.

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