scholarly journals Bacterial Quorum- sensing Signal Molecules as Potential Inhibitors of Cytokine Storms in COVID-19

2021 ◽  
Vol 1 (1) ◽  
pp. 162-165
Author(s):  
Ramakrishnan Sitaraman

In this perspective article, we suggest that bacterial quorum-sensing signal molecules (QSSMs) be systematically screened and evaluated for their ability to exert anti-inflammatory activity in the context of COVID-19-associated cytokine storms and other hyper-inflammatory conditions. Rapid and relevant in vitro screening of these and other compounds (natural or synthetic) can be accomplished by a careful choice of assay systems that are relevant to the disease context. Some lines of evidence indicating the utility of using such an approach, its potential benefits and risks during actual usage, as well as avenues for further research, are discussed.

2007 ◽  
Vol 362 (1483) ◽  
pp. 1223-1233 ◽  
Author(s):  
Ian Joint ◽  
Karen Tait ◽  
Glen Wheeler

The green seaweed Ulva has been shown to detect signal molecules produced by bacteria. Biofilms that release N -acylhomoserine lactones (AHLs) attract zoospores—the motile reproductive stages of Ulva . The evidence for AHL involvement is based on several independent lines of evidence, including the observation that zoospores are attracted to wild-type bacteria that produce AHLs but are not attracted to mutants that do not produce signal molecules. Synthetic AHL also attracts zoospores and the attraction is lost in the presence of autoinducer inactivation (AiiA) protein. The mechanism of attraction is not chemotactic but involves chemokinesis. When zoospores detect AHLs, the swimming rate is reduced and this results in accumulation of cells at the source of the AHL. It has been demonstrated that the detection of AHLs results in calcium influx into the zoospore. This is the first example of a calcium signalling event in a eukaryote in response to bacterial quorum sensing molecules. The role of AHLs in the ecology of Ulva is discussed. It is probable that AHLs act as cues for the settlement of zoospores, rather than being directly involved as a signalling mechanism.


2005 ◽  
Vol 187 (24) ◽  
pp. 8427-8436 ◽  
Author(s):  
Neela D. Keshavan ◽  
Puneet K. Chowdhary ◽  
Donovan C. Haines ◽  
Juan E. González

ABSTRACT Sinorhizobium meliloti is a gram-negative soil bacterium, capable of establishing a nitrogen-fixing symbiosis with its legume host, alfalfa (Medicago sativa). Quorum sensing plays a crucial role in this symbiosis, where it influences the nodulation process and the synthesis of the symbiotically important exopolysaccharide II (EPS II). S. meliloti has three quorum-sensing systems (Sin, Tra, and Mel) that use N-acyl homoserine lactones as their quorum-sensing signal molecule. Increasing evidence indicates that certain eukaryotic hosts involved in symbiotic or pathogenic relationships with gram-negative bacteria produce quorum-sensing-interfering (QSI) compounds that can cross-communicate with the bacterial quorum-sensing system. Our studies of alfalfa seed exudates suggested the presence of multiple signal molecules capable of interfering with quorum-sensing-regulated gene expression in different bacterial strains. In this work, we choose one of these QSI molecules (SWI) for further characterization. SWI inhibited violacein production, a phenotype that is regulated by quorum sensing in Chromobacterium violaceum. In addition, this signal molecule also inhibits the expression of the S. meliloti exp genes, responsible for the production of EPS II, a quorum-sensing-regulated phenotype. We identified this molecule as l-canavanine, an arginine analog, produced in large quantities by alfalfa and other legumes.


2018 ◽  
Author(s):  
Olena Moshynets ◽  
Lidia M. Babenko ◽  
Sergiy P. Rogalsky ◽  
Olga S. Iungin ◽  
Jessica Foster ◽  
...  

Several model plants are known to respond to bacterial quorum sensing molecules with altered root growth and gene expression patterns and induced resistance to plant pathogens. These compounds may represent novel elicitors that could be applied as seed primers to enhance cereal crop resistance to pathogens and abiotic stress and to improve yields. We investigated whether the acyl-homoserine lactone N-hexanoyl-L-homoserine lactone (C6-HSL) impacted winter wheat (Triticum aestivum L.) seed germination, plant development and productivity, using two Ukrainian varieties, Volodarka and Yatran 60, in both in vitro experiments and field trials. In vitro germination experiments indicated that C6-HSL seed priming had a small but significant positive impact on germination levels (1.2x increase, p < 0.0001), coleoptile and radicle development (1.4x increase, p < 0.0001). Field trials over two growing seasons (2015-16 and 2016-17) also demonstrated significant improvements in biomass at the tillering stage (1.4x increase, p < 0.0001), and crop structure and productivity at maturity including grain yield (1.4 – 1.5x increase, p < 0.0007) and quality (1.3x increase in good grain, p < 0.0001). In some cases variety effects were observed (p ≤ 0.05) suggesting that the effect of C6-HSL seed priming might depend on plant genetics, and some benefits of priming were also evident in F1 plants grown from seeds collected the previous season (p ≤ 0.05). These field-scale findings suggest that bacterial acyl-homoserine lactones such as C6-HSL could be used to improve cereal crop growth and yield and reduce reliance on fungicides and fertilisers to combat pathogens and stress.


2019 ◽  
Author(s):  
Justin E. Silpe ◽  
Bonnie L. Bassler

AbstractQuorum sensing (QS) is a process of cell-to-cell communication that bacteria use to orchestrate collective behaviors. QS relies on the cell-density-dependent production, accumulation, and receptor-mediated detection of extracellular signaling molecules called autoinducers (AIs). Gram-negative bacteria commonly use N-acyl homoserine lactones (AHLs) as their AIs and they are detected by LuxR-type receptors. Often, LuxR-type receptors are insoluble when not bound to a cognate AI. In this report, we show that LuxR-type receptors are encoded on phage genomes and, in the cases we tested, the phage LuxR-type receptors bind to and are solubilized specifically by the AHL AI produced by the host bacterium. We do not yet know the viral activities that are controlled by these phage QS receptors, however, our observations, coupled with recent reports, suggest that their occurrence is more widespread than previously appreciated. Using receptor-mediated detection of QS AIs could enable phages to garner information concerning the population density status of their bacterial hosts. We speculate that such information can be exploited by phages to optimize the timing of execution of particular steps in viral infection.ImportanceBacteria communicate with chemical signal molecules to regulate group behaviors in a process called quorum sensing (QS). In this report, we find that genes encoding receptors for Gram-negative bacterial QS communication molecules are present on genomes of viruses that infect these bacteria. These viruses are called phages. We show that two phage-encoded receptors, like their bacterial counterparts, bind to the communication molecule produced by the host bacterium, suggesting that phages can “listen in” on their bacterial hosts. Interfering with bacterial QS and using phages to kill pathogenic bacteria represent attractive possibilities for development of new antimicrobials to combat pathogens that are resistant to traditional antibiotics. Our findings of interactions between phages and QS bacteria need consideration as new antimicrobial therapies are developed.


2006 ◽  
Vol 70 (4) ◽  
pp. 859-875 ◽  
Author(s):  
Juan E. González ◽  
Neela D. Keshavan

SUMMARY Quorum sensing is widely recognized as an efficient mechanism to regulate expression of specific genes responsible for communal behavior in bacteria. Several bacterial phenotypes essential for the successful establishment of symbiotic, pathogenic, or commensal relationships with eukaryotic hosts, including motility, exopolysaccharide production, biofilm formation, and toxin production, are often regulated by quorum sensing. Interestingly, eukaryotes produce quorum-sensing-interfering (QSI) compounds that have a positive or negative influence on the bacterial signaling network. This eukaryotic interference could result in further fine-tuning of bacterial quorum sensing. Furthermore, recent work involving the synthesis of structural homologs to the various quorum-sensing signal molecules has resulted in the development of additional QSI compounds that could be used to control pathogenic bacteria. The creation of transgenic plants that express bacterial quorum-sensing genes is yet another strategy to interfere with bacterial behavior. Further investigation on the manipulation of quorum-sensing systems could provide us with powerful tools against harmful bacteria.


2020 ◽  
Author(s):  
Erin Higgins ◽  
Julian Kellner-Rogers ◽  
Alexandra Estanislau ◽  
Alec Esposito ◽  
Nora R. Vail ◽  
...  

<p>Quorum sensing is a bacterial signaling system that involves the synthesis and subsequent detection of small signal molecules called autoinducers. The main autoinducer in gram-negative bacteria are acylated homoserine lactones (AHLs), produced by LuxI autoinducer synthase enzymes and detected by LuxR autoinducer receptors. Quorum sensing allows for changes in gene expression resulting bacterial behavior in a coordinated, cell-density dependent fashion. Some of the behaviors controlled by quorum sensing involve pathogenesis, making quorum sensing signaling a target to develop new antibacterial agents. Here we describe the design and synthesis of transition-state analogs of the autoinducer synthase enzymatic reaction and the evaluation of these compounds as inhibitors of the synthase CepI. One such compound potently inhibits CepI and constitutes a new type of inhibitor against this underdeveloped antibacterial target.</p>


2003 ◽  
Vol 58 (11-12) ◽  
pp. 879-884 ◽  
Author(s):  
Birgit Huber ◽  
Leo Eberl ◽  
Walter Feucht ◽  
Jürgen Polster

Abstract Many bacteria utilize sophisticated regulatory systems to ensure that some functions are only expressed when a particular population density has been reached. The term ‘quorumsensing’ has been coined to describe this form of density-dependent gene regulation which relies on the production and perception of small signal molecules by bacterial cells. As in many pathogenic bacteria the production of virulence factors is quorum-sensing regulated, it has been suggested that this form of gene regulation allows the bacteria to remain invisible to the defence systems of the host until the population is sufficiently large to successfully establish the infection. Here we present first evidence that polyphenolic compounds can interfere with bacterial quorum-sensing. Since polyphenols are widely distributed in the plant kingdom, they may be important for promoting plant fitness.


mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Justin E. Silpe ◽  
Bonnie L. Bassler

ABSTRACT Quorum sensing (QS) is a process of cell-to-cell communication that bacteria use to orchestrate collective behaviors. QS relies on the cell-density-dependent production, accumulation, and receptor-mediated detection of extracellular signaling molecules called autoinducers (AIs). Gram-negative bacteria commonly use N-acyl homoserine lactones (AHLs) as their AIs, and they are detected by LuxR-type receptors. Often, LuxR-type receptors are insoluble when not bound to a cognate AI. In this report, we show that LuxR-type receptors are encoded on phage genomes, and in the cases we tested, the phage LuxR-type receptors bind to and are solubilized specifically by the AHL AI produced by the host bacterium. We do not yet know the viral activities that are controlled by these phage QS receptors; however, our observations, coupled with recent reports, suggest that their occurrence is more widespread than previously appreciated. Using receptor-mediated detection of QS AIs could enable phages to garner information concerning the population density status of their bacterial hosts. We speculate that such information can be exploited by phages to optimize the timing of execution of particular steps in viral infection. IMPORTANCE Bacteria communicate with chemical signal molecules to regulate group behaviors in a process called quorum sensing (QS). In this report, we find that genes encoding receptors for Gram-negative bacterial QS communication molecules are present on genomes of viruses that infect these bacteria. These viruses are called phages. We show that two phage-encoded receptors, like their bacterial counterparts, bind to the communication molecule produced by the host bacterium, suggesting that phages can “listen in” on their bacterial hosts. Interfering with bacterial QS and using phages to kill pathogenic bacteria represent attractive possibilities for development of new antimicrobials to combat pathogens that are resistant to traditional antibiotics. Our findings of interactions between phages and QS bacteria need consideration as new antimicrobial therapies are developed.


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