scholarly journals Coumarin’s Anti-Quorum Sensing Activity Can Be Enhanced When Combined with Other Plant-Derived Small Molecules

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 208
Author(s):  
Dmitry Deryabin ◽  
Kseniya Inchagova ◽  
Elena Rusakova ◽  
Galimzhan Duskaev
Keyword(s):  
Quorum Sensing ◽  
Small Molecules ◽  
Bacterial Communities ◽  
Cell Communication ◽  
Small Plant ◽  
Eucalyptus Leaves ◽  
Eucalyptus Viminalis ◽  
Fold Reduction ◽  
Half Maximal Effective Concentration ◽  
Violacein Production

Coumarins are class of natural aromatic compounds based on benzopyrones (2H-1-benzopyran-2-ones). They are identified as secondary metabolites in about 150 different plant species. The ability of coumarins to inhibit cell-to-cell communication in bacterial communities (quorum sensing; QS) has been previously described. Coumarin and its derivatives in plant extracts are often found together with other small molecules that show anti-QS properties too. The aim of this study was to find the most effective combinations of coumarins and small plant-derived molecules identified in various plants extracts that inhibit QS in Chromobacterium violaceum ATCC 31532 violacein production bioassay. The coumarin and its derivatives: 7-hydroxycoumarin, 7.8-dihydroxy-4-methylcoumarin, were included in the study. Combinations of coumarins with gamma-octalactone, 4-hexyl-1.3-benzenediol, 3.4.5-trimethoxyphenol and vanillin, previously identified in oak bark (Quercus cortex), and eucalyptus leaves (Eucalyptus viminalis) extracts, were analyzed in a bioassay. When testing two-component compositions, it was shown that 7.8-dihydroxy-4-methylcoumarin, 4-hexyl-1.3-benzendiol, and gamma-octalactone showed a supra-additive anti-QS effect. Combinations of all three molecules resulted in a three- to five-fold reduction in the concentration of each compound needed to achieve EC50 (half maximal effective concentration) against QS in C. violaceum ATCC 31532.

Rapid Characterization of Quorum Sensing Inhibitory Molecules from Garcinia indica Choisy Seed Methanol Extract by GC-MS Analysis

2020 ◽  
Vol 16 (6) ◽  
pp. 887-891 ◽  
Author(s):  
Rajesh P. Shastry ◽  
Mohammed Aman
Keyword(s):  
Quorum Sensing ◽  
Methanol Extract ◽  
Cell Communication ◽  
Garcinia Indica ◽  
Biosensor Strain ◽  
Bioactive Fraction ◽  
Violacein Production ◽  
Rapid Characterization ◽  
Inhibitory Molecules

Background: Bacteria communicate by producing small signaling molecules to maintain threshold cell density. Quorum sensing inhibition is an effective and most potent approach for the prevention of cell to cell communication. Methods: In the present study, the methanol extract of Garcinia indica was tested for anti-quorum sensing activity using Chromobacterium violaceum as a biosensor. The extract inhibited violacein production in biosensor strain without affecting the growth of the bacteria and this was corroborated by bioautography assay. Results: The bioactive fraction was analysed by the aid of GC-MS revealed that, the presence of coumarin (7-hydroxy-3-(1,1-dimethylprop-2-enyl) coumarin) and eugenol (1,2-dimethoxy-4-(1-methoxy-1- propenyl) benzene) derivatives as anti-quorum sensing molecules. Conclusion: A detailed investigation is required to study the mechanism of action involved in control of quorum sensing signals and possible applications.

scholarly journals Involvement of a Quorum Sensing Signal Molecule in the Extracellular Amylase Activity of the Thermophilic Anoxybacillus amylolyticus

2021 ◽  
Vol 9 (4) ◽  
pp. 819
Author(s):  
Annabella Tramice ◽  
Adele Cutignano ◽  
Annalaura Iodice ◽  
Annarita Poli ◽  
Ilaria Finore ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Small Molecules ◽  
Amylase Activity ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Signal Molecule ◽  
Thermophilic Microorganism ◽  
Thermophilic Microorganisms ◽  
Homoserine Lactones ◽  
And Diffusion

Anoxybacillus amylolyticus is a moderate thermophilic microorganism producing an exopolysaccharide and an extracellular α-amylase able to hydrolyze starch. The synthesis of several biomolecules is often regulated by a quorum sensing (QS) mechanism, a chemical cell-to-cell communication based on the production and diffusion of small molecules named “autoinducers”, most of which belonging to the N-acyl homoserine lactones’ (AHLs) family. There are few reports about this mechanism in extremophiles, in particular thermophiles. Here, we report the identification of a signal molecule, the N-butanoyl-homoserine lactone (C4-HSL), from the milieu of A. amylolyticus. Moreover, investigations performed by supplementing a known QS inhibitor, trans-cinnamaldehyde, or exogenous C4-HSL in the growth medium of A. amylolyticus suggested the involvement of QS signaling in the modulation of extracellular α-amylase activity. The data showed that the presence of the QS inhibitor trans-cinnamaldehyde in the medium decreased amylolytic activity, which, conversely, was increased by the effect of exogenous C4-HSL. Overall, these results represent the first evidence of the production of AHLs in thermophilic microorganisms, which could be responsible for a communication system regulating thermostable α-amylase activity.

Gap junctions in the prothoracic glands of the tobacco hornworm, Manduca sexta

1992 ◽  
Vol 50 (1) ◽  
pp. 706-707
Author(s):  
Ji-da Dai ◽  
M. Joseph Costello ◽  
Lawrence I. Gilbert
Keyword(s):  
Gap Junctions ◽  
Small Molecules ◽  
Manduca Sexta ◽  
Freeze Fracture ◽  
Cell Communication ◽  
Cellular Level ◽  
Thin Sections ◽  
Prothoracic Glands ◽  
Polyhydroxylated Steroids ◽  
Stimulation Of

Insect molting and metamorphosis are elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands (PGs). Prothoracicotropic hormone stimulation of steroidogenesis by the PGs at the cellular level involves both calcium and cAMP. Cell-to-cell communication mediated by gap junctions may play a key role in regulating signal transduction by controlling the transmission of small molecules and ions between adjacent cells. This is the first report of gap junctions in the PGs, the evidence obtained by means of SEM, thin sections and freeze-fracture replicas.

Quorum Sensing – A Stratagem for Conquering Multi-Drug Resistant Pathogens

2020 ◽  
Vol 26 ◽  
Author(s):  
Madison Tonkin ◽  
Shama Khan ◽  
Mohmmad Younus Wani ◽  
Aijaz Ahmad
Keyword(s):  
Drug Resistance ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Cell Communication ◽  
Natural Compounds ◽  
Quorum Sensing Inhibitors ◽  
Communication Technique ◽  
Multicellular Organisms ◽  
Chemical Strategies

: Quorum sensing is defined as cell to cell communication between microorganisms, which enables microorganisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing as well as biofilm formation encourage the development of drug resistance in microorganisms. Biofilm formation and quorum sensing are causally linked to each other and play role in the pathogenesis of microorganisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the microorganisms. This review encompasses the communication technique used by microorganisms, how microorganism resistance is linked to quorum sensing and various chemical strategies to combat quorum sensing and thereby drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds present several related disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that anti-quorum sensing compounds are effective in disrupting quorum sensing and could therefore be effective in reducing microorganism drug resistance.

scholarly journals A Cellular Assay for the Identification and Characterization of Connexin Gap Junction Modulators

2021 ◽  
Vol 22 (3) ◽  
pp. 1417
Author(s):  
Azeem Danish ◽  
Robin Gedschold ◽  
Sonja Hinz ◽  
Anke C. Schiedel ◽  
Dominik Thimm ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Small Molecules ◽  
High Throughput Screening ◽  
Cell Communication ◽  
Receptor Activation ◽  
Adenosine A2a Receptor ◽  
Intracellular Camp ◽  
Donor Cells ◽  
A2a Receptor ◽  
Adenosine A2a

Connexin gap junctions (Cx GJs) enable the passage of small molecules and ions between cells and are therefore important for cell-to-cell communication. Their dysfunction is associated with diseases, and small molecules acting as modulators of GJs may therefore be useful as therapeutic drugs. To identify GJ modulators, suitable assays are needed that allow compound screening. In the present study, we established a novel assay utilizing HeLa cells recombinantly expressing Cx43. Donor cells additionally expressing the Gs protein-coupled adenosine A2A receptor, and biosensor cells expressing a cAMP-sensitive GloSensor luciferase were established. Adenosine A2A receptor activation in the donor cells using a selective agonist results in intracellular cAMP production. The negatively charged cAMP migrates via the Cx43 gap junctions to the biosensor cells and can there be measured by the cAMP-dependent luminescence signal. Cx43 GJ modulators can be expected to impact the transfer of cAMP from the donor to the biosensor cells, since cAMP transit is only possible via GJs. The new assay was validated by testing the standard GJ inhibitor carbenoxolon, which showed a concentration-dependent inhibition of the signal and an IC50 value that was consistent with previously reported values. The assay was demonstrated to be suitable for high-throughput screening.

scholarly journals Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Orit Malka ◽  
Dorin Kalson ◽  
Karin Yaniv ◽  
Reut Shafir ◽  
Manikandan Rajendran ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Gut Microbiome ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Human Microbiome ◽  
Cell Communication ◽  
Probiotic Yeast ◽  
Gut Pathogen ◽  
Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

scholarly journals N-3-Hydroxy Dodecanoyl-DL-homoserine Lactone (OH-dDHL) Triggers Apoptosis of Bone Marrow-Derived Macrophages through the ER- and Mitochondria-Mediated Pathways

2021 ◽  
Vol 22 (14) ◽  
pp. 7565
Author(s):  
Kyungho Woo ◽  
Dong Ho Kim ◽  
Man Hwan Oh ◽  
Ho Sung Park ◽  
Chul Hee Choi
Keyword(s):  
Bone Marrow ◽  
Quorum Sensing ◽  
Deletion Mutant ◽  
Transmembrane Protein ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Host Responses ◽  
Wild Type ◽  
Mutant Strains

Quorum sensing of Acinetobacter nosocomialis for cell-to-cell communication produces N-3-hydroxy dodecanoyl-DL-homoserine lactone (OH-dDHL) by an AnoR/I two-component system. However, OH-dDHL-driven apoptotic mechanisms in hosts have not been clearly defined. Here, we investigated the induction of apoptosis signaling pathways in bone marrow-derived macrophages treated with synthetic OH-dDHL. Moreover, the quorum-sensing system for virulence regulation was evaluated in vivo using wild-type and anoI-deletion mutant strains. OH-dDHL decreased the viability of macrophage and epithelial cells in dose- and time-dependent manners. OH-dDHL induced Ca2+ efflux and caspase-12 activation by ER stress transmembrane protein (IRE1 and ATF6a p50) aggregation and induced mitochondrial dysfunction through reactive oxygen species (ROS) production, which caused cytochrome c to leak. Pretreatment with a pan-caspase inhibitor reduced caspase-3, -8, and -9, which were activated by OH-dDHL. Pro-inflammatory cytokine and paraoxonase-2 (PON2) gene expression were increased by OH-dDHL. We showed that the anoI-deletion mutant strains have less intracellular invasion compared to the wild-type strain, and their virulence, such as colonization and dissemination, was decreased in vivo. Consequently, these findings revealed that OH-dDHL, as a virulence factor, contributes to bacterial infection and survival as well as the modification of host responses in the early stages of infection.

scholarly journals Anti-biofilm and Virulence Factor-Reducing Activities of Essential Oils and Oil Components as a Possible Option for Bacterial Infection Control

Planta Medica ◽  
2020 ◽  
Vol 86 (08) ◽  
pp. 520-537 ◽  
Author(s):  
Jürgen Reichling
Keyword(s):  
Quorum Sensing ◽  
Essential Oil ◽  
Essential Oils ◽  
Virulence Factor ◽  
Model Organisms ◽  
Regulation System ◽  
Expression Of Genes ◽  
Reporter Strains ◽  
Violacein Production ◽  
Essential Oil Compounds

AbstractPathogenic biofilm-associated bacteria that adhere to biological or nonbiological surfaces are a big challenge to the healthcare and food industries. Antibiotics or disinfectants often fail in an attempt to eliminate biofilms from those surfaces. Based on selected experimental research, this review deals with the potential biofilm-inhibiting, virulence factor-reducing, and biofilm-eradicating activities of essential oils and single essential oil compounds using Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Chromobacterium violaceum as model organisms. In addition, for the bacteria reviewed in this overview, different essential oils and essential oil compounds were reported to be able to modulate the expression of genes that are involved in the formation of autoinducer molecules, biofilms, and virulence factors. The anti-quorum sensing activity of some essential oils and single essential oil compounds was demonstrated using the gram-negative bacterium C. violaceum. Reporter strains of this bacterium produce the violet-colored compound violacein whose synthesis is regulated by quorum sensing autoinducer molecules called acylhomeserinlactones. Of great interest was the discovery that enantiomeric monoterpenes affected the quorum sensing regulation system in different ways. While the (+)-enantiomers of carvone, limonene, and borneol increased violacein formation, their (−)-analogues inhibited violacein production.For the successful eradication of biofilms and the bacteria living inside them, it is absolutely necessary that the lipophilic volatile substances can penetrate into the aqueous channels of biofilms. As shown in recent work, hydrophilic nano-delivery systems encapsulating essential oils/essential oil compounds with antibacterial effects may contribute to overcome this problem.

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