Attenuation of quorum sensing-mediated virulence in Gram-negative pathogenic bacteria: implications for the post-antibiotic era

MedChemComm ◽  
2015 ◽  
Vol 6 (2) ◽  
pp. 259-272 ◽  
Author(s):  
Ravindra Pal Singh

Quorum quenching compounds blocked quorum sensing system of bacteria by several mechanisms (a, b, c and d).

2007 ◽  
Vol 189 (19) ◽  
pp. 7077-7088 ◽  
Author(s):  
Sarah A. Glenn ◽  
Nataliya Gurich ◽  
Morgan A. Feeney ◽  
Juan E. González

ABSTRACT Sinorhizobium meliloti is a gram-negative soil bacterium capable of forming a symbiotic nitrogen-fixing relationship with its plant host, Medicago sativa. Various bacterially produced factors are essential for successful nodulation. For example, at least one of two exopolysaccharides produced by S. meliloti (succinoglycan or EPS II) is required for nodule invasion. Both of these polymers are produced in high- and low-molecular-weight (HMW and LMW, respectively) fractions; however, only the LMW forms of either succinoglycan or EPS II are active in nodule invasion. The production of LMW succinoglycan can be generated by direct synthesis or through the depolymerization of HMW products by the action of two specific endoglycanases, ExsH and ExoK. Here, we show that the ExpR/Sin quorum-sensing system in S. meliloti is involved in the regulation of genes responsible for succinoglycan biosynthesis as well as in the production of LMW succinoglycan. Therefore, quorum sensing, which has been shown to regulate the production of EPS II, also plays an important role in succinoglycan biosynthesis.


Author(s):  
Nicole Hugouvieux‐Cotte‐Pattat ◽  
Monique Royer ◽  
Erwan Gueguen ◽  
Paul Le Guen ◽  
Roderich D. Süssmuth ◽  
...  

Author(s):  
Jesus M. Luna-Solorza ◽  
Francisco J. Vazquez-Armenta ◽  
A. Thalia Bernal-Mercado ◽  
M. Melissa Gutierrez-Pacheco ◽  
Filomena Nazzaro ◽  
...  

2009 ◽  
Vol 56 (1) ◽  
Author(s):  
Robert Czajkowski ◽  
Sylwia Jafra

Many Gram-positive and Gram-negative bacteria communicate using small diffusible signal molecules called autoinducers. This process, known as quorum sensing (QS), links cell density to the expression of genes as diverse as those associated with virulence factors production of plant and animal pathogens, bioluminescence, antibiotic production, sporulation or biofilm formation. In Gram-negative bacteria, this communication is mainly mediated by N-acyl-homoserine lactones (AHLs). It has been proven that inactivation of the signal molecules attenuates many of the processes controlled by QS. Enzymatic degradation of the signal molecules has been amply described. Two main classes of AHL-inactivating enzymes were identified: AHL lactonases which hydrolyse the lactone ring in AHLs, and AHL acylases (syn. AHL amidases) which liberate a free homoserine lactone and a fatty acid. Recently, AHL oxidoreductase, a novel type of AHL inactivating enzyme, was described. The activity of these enzymes results in silencing the QS-regulated processes, as degradation products cannot act as signal molecules. The ability to inactivate AHL (quorum quenching, QQ) might be useful in controlling virulence of many pathogenic bacteria.


Author(s):  
Korbin H. J. West ◽  
Wenqi Shen ◽  
Emma L. Eisenbraun ◽  
Tian Yang ◽  
Joseph K. Vasquez ◽  
...  

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S10-S10
Author(s):  
Artemis Gogos ◽  
Michael J Federle

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.


Author(s):  
Tommonaro Giuseppina ◽  
Abbamondi Gennaro Roberto ◽  
Toksoy Oner Ebru ◽  
Nicolaus Barbara

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