Synthetic strategies to access staphylococcus auto-inducing peptides as quorum sensing modulators

2020 ◽  
Vol 18 (3) ◽  
pp. 379-390 ◽  
Author(s):  
Christopher P. Gordon
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Accessory Gene ◽  
Sensing System ◽  
Accessory Gene Regulator ◽  
Quorum Sensing System ◽  
Important Regulator

The accessory gene regulator (agr) quorum-sensing system is arguably the most important regulator of staphylococcus virulence and has been the focus of tremendous interest in the development of effective therapies for pathogenic bacterial infections.

scholarly journals Identification of a Staphylococcal AgrB Segment(s) Responsible for Group-Specific Processing of AgrD by Gene Swapping

2004 ◽  
Vol 186 (20) ◽  
pp. 6706-6713 ◽  
Author(s):  
Linsheng Zhang ◽  
Guangyong Ji
Keyword(s):  
Quorum Sensing ◽  
Transmembrane Protein ◽  
Specific Interaction ◽  
Accessory Gene ◽  
Sensing System ◽  
Accessory Gene Regulator ◽  
Group I ◽  
Quorum Sensing System ◽  
Group Ii ◽  
Α Helix

ABSTRACT The four gene products of the accessory gene regulator (agr) P2 operon of Staphylococcus aureus assemble a quorum-sensing system: AgrA and AgrC resemble a two-component signal transduction system, and AgrB and AgrD are required to produce an autoinducing peptide. Upon activation, this quorum-sensing system positively regulates the transcription of the P2 operon as well as the P3 operon, whose transcript, RNAIII, regulates the expression of virulence genes. Four groups of S. aureus have been identified based on the agr sequences and the group-specific interaction between the autoinducing peptide and AgrC. AgrB is a transmembrane protein involved in the processing of AgrD propeptide, and its interaction with AgrD is also group specific. In this study, a series of chimeric AgrBs were constructed by swapping between group I and group II AgrBs, and these mutants were used to analyze the group-specific segment(s) in AgrB that was responsible for AgrD processing. Our results revealed that the first transmembrane α-helix and the extracellular loop 1 of group I AgrB were decisive in the specific processing of group I AgrD. In contrast, two hydrophilic segments of group II AgrB played a crucial role in the group-specific processing of group II AgrD. We also found that several chimeric AgrBs were capable of processing AgrD from both groups, suggesting that all AgrB homologues may utilize the same or a similar mechanism in the processing of AgrDs.

Quorum sensing system: Target to control the spread of bacterial infections

2020 ◽  
Vol 142 ◽  
pp. 104068 ◽  
Author(s):  
Erika Kushikawa Saeki ◽  
Renata Katsuko Takayama Kobayashi ◽  
Gerson Nakazato
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Sensing System ◽  
Quorum Sensing System

scholarly journals Rot Repression of Enterotoxin B Expression in Staphylococcus aureus

2005 ◽  
Vol 187 (15) ◽  
pp. 5301-5309 ◽  
Author(s):  
Ching Wen Tseng ◽  
George C. Stewart
Keyword(s):  
Staphylococcus Aureus ◽  
Exponential Phase ◽  
Regulatory Pathway ◽  
Accessory Gene ◽  
Sensing System ◽  
Accessory Gene Regulator ◽  
Quorum Sensing System ◽  
Associated Proteins ◽  
Enterotoxin B ◽  
Repressor Activity

ABSTRACT The accessory gene regulator (Agr) system is a quorum-sensing system of Staphylococcus aureus responsible for upregulation of certain exoprotein genes and downregulation of certain cell-wall associated proteins during the post-exponential phase of growth. The enterotoxin B (seb) determinant is upregulated by the Agr system. Agr-regulated cis elements within the seb promoter region were examined by deletion analyses of the seb promoter by a hybrid promoter approach utilizing the staphylococcal lac operon promoter. To identify the regulatory pathway for enterotoxin B expression, the seb promoter fused to the chloramphenicol acetyltransferase reporter gene was introduced into mutants of S. aureus lacking agr or different members of the Sar family of transcriptional regulators. Agr control of seb promoter activity was found to be dependent upon the presence of a functional Rot protein, and Rot was shown to be able to bind to the seb promoter. Therefore, the Agr-mediated post-exponential-phase increase in seb transcription results from the Agr system's inactivation of Rot repressor activity.

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

#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.

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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