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1.
Quorum sensing (QS) has traditionally referred to a mechanism of communication within a species of bacteria. However, emerging research implicates QS in interspecies communication and competition, and such systems have been proposed in a wide variety of bacteria. This activity of bacterial QS also extends to relationships between bacteria and eukaryotes and host-pathogen interactions in both clinical and agricultural settings are of particular interest. These relationships are particularly pertinent in light of the rising prevalence of antibiotic resistant bacteria. In this tutorial review we describe bacterial QS and its capacity in interspecies and interkingdom interactions, as well as the corresponding eukaryotic responses. 相似文献
2.
K Tsuchikama J Zhu CA Lowery GF Kaufmann KD Janda 《Journal of the American Chemical Society》2012,134(33):13562-13564
Bacteria have developed cell-to-cell communication mechanisms, termed quorum sensing (QS), that regulate bacterial gene expression in a cell population-dependent manner. Autoinducer-2 (AI-2), a class of QS signaling molecules derived from (4S)-4,5-dihydroxy-2,3-pentanedione (DPD), has been identified in both Gram-negative and Gram-positive bacteria. Despite considerable interest in the AI-2 QS system, the biomolecular communication used by distinct bacterial species still remains shrouded. Herein, we report the synthesis and evaluation of a new class of DPD analogues, C4-alkoxy-5-hydroxy-2,3-pentanediones, termed C4-alkoxy-HPDs. Remarkably, two of the analogues were more potent QS agonists than the natural ligand, DPD, in Vibrio harveyi. The findings presented extend insights into ligand-receptor recognition/signaling in the AI-2 mediated QS system. 相似文献
3.
Bacteria have developed a cell-to-cell communication system, termed quorum sensing (QS), which allows for the population-dependent coordination of their behavior via the exchange of chemical signals. Autoinducer-2 (AI-2), a class of QS signals derived from 4,5-dihydroxy-2,3-pentandione (DPD), has been revealed as a universal signaling molecule in a variety of bacterial species. In spite of considerable interest, the study of putative AI-2 based QS systems remains a challenging topic in part due to the rapid interconversion between the linear and cyclic forms of DPD. Herein, we report the design and development of efficient syntheses of carbocyclic analogues of DPD, which are locked in the cyclic form. The synthetic analogues were evaluated for the modulation of AI-2-based QS in Vibrio harveyi and Salmonella typhimurium. No agonists were uncovered in either V. harveyi or S. typhimurium assay, whereas weak to moderate antagonists were found against V. harveyi. On the basis of NMR analyses and DFT calculations, the heterocyclic oxygen atom within DPD appears necessary to promote hydration at the C3 position of cyclic DPD to afford the active tetrahydroxy species. These results also shed light on the interaction between the heterocyclic oxygen atom and receptor proteins as well as the importance of the linear form and dynamic equilibrium of DPD as crucial requirements for activation of AI-2 based QS circuits. 相似文献
4.
Victor Markus Karina Golberg Kerem Teral Nazmi Ozer Esti Kramarsky-Winter Robert S. Marks Ariel Kushmaro 《Molecules (Basel, Switzerland)》2021,26(6)
Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date. 相似文献
5.
[reaction: see text] The unstable bacterial metabolic product, DPD, and the related natural product, laurencione, are shown to have a high affinity for borate complexation, through the hydrated analogue. The boron complex of DPD is Vibrio harveyi AI-2, an interspecies quorum sensing signal in bacteria, and an affinity column with a borate resin is effective in providing the first method for concentrating and purifying V. harveyi AI-2 from the biosynthetic product. 相似文献
6.
Rumbaugh KP 《Analytical and bioanalytical chemistry》2007,387(2):425-435
Most living organisms possess sophisticated cell-signaling networks in which lipid-based signals modulate biological effects
such as cell differentiation, reproduction and immune responses. Acyl homoserine lactone (AHL) autoinducers are fatty acid-based
signaling molecules synthesized by several Gram-negative bacteria that are used to coordinate gene expression in a process
termed “quorum sensing” (QS). Recent evidence shows that autoinducers not only control gene expression in bacterial cells,
but also alter gene expression in mammalian cells. These alterations include modulation of proinflammatory cytokines and induction
of apoptosis. Some of these responses may have deleterious effects on the host’s immune response, thereby leading to increased
bacterial pathogenesis. Prokaryotes and eukaryotes have cohabited for approximately two billion years, during which time they
have been exposed to each others’ soluble signaling molecules. We postulate that organisms from the different kingdoms of
nature have acquired mechanisms to sense and respond to each others signaling molecules, and we have named this process interkingdom
signaling. We further propose that autoinducers, which exhibit structural and functional similarities to mammalian lipid-based
hormones, are excellent candidates for mediating this interkingdom communication. Here we will compare and contrast bacterial
QS systems with eukaryotic endocrine systems, and discuss the mechanisms by which autoinducers may exploit mammalian signal
transduction pathways. 相似文献
7.
Bacteria are able to coordinate gene expression as a community through the secretion and detection of signalling molecules
so that the members of the community can simultaneously express specific behaviours. This mechanism of regulation of behaviour
appears to be a key trait for adaptation to specific environments and has been shown to regulate a variety of important phenotypes,
from virulence factor production to biofilm formation to symbiosis related behaviours such as bioluminescence. The ability
to communicate and communally regulate gene expression is hypothesised to have evolved as a way for organisms to delay expression
of phenotypes until numerical supremacy is reached. For example, in the case of infection, if an invading microorganism were
to express virulence factors too early, the host may be able to mount a successful defence and repel the invaders. There is
growing evidence that bacterial quorum sensing (QS) systems are involved in cross-kingdom signalling with eukaryotic organisms
and that eukaryotes are capable of actively responding to bacteria in their environment by detecting and acting upon the presence
of these signalling molecules. Likewise, eukaryotes produce compounds that can interfere with QS systems in bacteria by acting
as agonists or antagonists. An exciting new field of study, biomimetics, takes inspiration from nature’s models and attempts
to design solutions to human problems, and biomimics of QS systems may be one such solution. This article presents the acylated
homoserine lactone and autoinducer 2 QS systems in bacteria, the means of intercepting or interfering with bacterial QS systems
evolved by eukaryotes, and the rational design of synthetic antagonists.
Figure Natural products, furanones, from the red alga Delisea pulchra inhibit the quorum sensing regulated production of violacein by Chromobacterium violaceum
“The proof of evolution lies in those adaptations that arise from improbable foundations”—Stephen Jay Gould 相似文献
8.
The term quorum sensing (QS) refers to the ability of bacteria to regulate gene expression according to the accumulation of
signalling molecules that are made by every cell in the population. The erwiniae group of bacteria are often phytopathogens
and the expression of a number of their important virulence determinants and secondary metabolites is under QS control. The
erwiniae utilise two types of QS signalling molecules: N-acyl homoserine lactones and AI-2-type signalling molecules. Here, we review the regulatory networks involving QS in the
soft rot erwiniae. 相似文献
9.
Quorum sensing (QS) is a bacterial communication using signal molecules, by which they sense population density of their own species, leading to group behavior such as biofilm formation and virulence. Autoinducer-2 (AI2) is a QS signal molecule universally used by both gram-positive and gram-negative bacteria. Inhibition of QS mediated by AI2 is important for various practical applications, including prevention of gum-disease caused by biofilm formation of oral bacteria. In this research, molecular docking and molecular dynamics (MD) simulations were performed for molecules that are chemically similar to known AI2 inhibitors that might have a potential to be quorum sensing inhibitors. The molecules that form stable complexes with the AI2 receptor protein were found, suggesting that they could be developed as a novel AI2 inhibitors after further in vitro validation. The result suggests that combination of ligand-based drug design and computational methods such as MD simulation, and experimental verification, may lead to development of novel AI inhibitor, with a broad range of practical applications. 相似文献
10.
Struss AK Pasini P Flomenhoft D Shashidhar H Daunert S 《Analytical and bioanalytical chemistry》2012,402(10):3227-3236
Quorum sensing (QS) allows bacteria to communicate with one another by means of QS signaling molecules and control certain
behaviors in a group-based manner, including pathogenicity and biofilm formation. Bacterial gut microflora may play a role
in inflammatory bowel disease pathogenesis, and antibiotics are one of the available therapeutic options for Crohn’s disease.
In the present study, we employed genetically engineered bioluminescent bacterial whole-cell sensing systems as a tool to
evaluate the ability of antibiotics commonly employed in the treatment of chronic inflammatory conditions to interfere with
QS. We investigated the effect of ciprofloxacin, metronidazole, and tinidazole on quorum sensing. Several concentrations of
individual antibiotics were allowed to interact with two different types of bacterial sensing cells, in both the presence
and absence of a fixed concentration of N-acylhomoserine lactone (AHL) QS molecules. The antibiotic effect was then determined by monitoring the biosensor’s bioluminescence
response. Ciprofloxacin, metronidazole, and tinidazole exhibited a dose-dependent augmentation in the response of both bacterial
sensing systems, thus showing an AHL-like effect. Additionally, such an augmentation was observed, in both the presence and
absence of AHL. The data obtained indicate that ciprofloxacin, metronidazole, and tinidazole may interfere with bacterial
communication systems. The results suggest that these antibiotics, at the concentrations tested, may themselves act as bacterial
signaling molecules. The beneficial effect of these antibiotics in the treatment of intestinal inflammation may be due, at
least in part, to their effect on QS-related bacterial behavior in the gut. 相似文献
11.
Abdelhakim Bouyahya Imane Chamkhi Abdelaali Balahbib Maksim Rebezov Mohammad Ali Shariati Polrat Wilairatana Mohammad S. Mubarak Taoufiq Benali Nasreddine El Omari 《Molecules (Basel, Switzerland)》2022,27(5)
Bacterial strains have developed an ability to resist antibiotics via numerous mechanisms. Recently, researchers conducted several studies to identify natural bioactive compounds, particularly secondary metabolites of medicinal plants, such as terpenoids, flavonoids, and phenolic acids, as antibacterial agents. These molecules exert several mechanisms of action at different structural, cellular, and molecular levels, which could make them candidates or lead compounds for developing natural antibiotics. Research findings revealed that these bioactive compounds can inhibit the synthesis of DNA and proteins, block oxidative respiration, increase membrane permeability, and decrease membrane integrity. Furthermore, recent investigations showed that some bacterial strains resist these different mechanisms of antibacterial agents. Researchers demonstrated that this resistance to antibiotics is linked to a microbial cell-to-cell communication system called quorum sensing (QS). Consequently, inhibition of QS or quorum quenching is a promising strategy to not only overcome the resistance problems but also to treat infections. In this respect, various bioactive molecules, including terpenoids, flavonoids, and phenolic acids, exhibit numerous anti-QS mechanisms via the inhibition of auto-inducer releases, sequestration of QS-mediated molecules, and deregulation of QS gene expression. However, clinical applications of these molecules have not been fully covered, which limits their use against infectious diseases. Accordingly, the aim of the present work was to discuss the role of the QS system in bacteria and its involvement in virulence and resistance to antibiotics. In addition, the present review summarizes the most recent and relevant literature pertaining to the anti-quorum sensing of secondary metabolites and its relationship to antibacterial activity. 相似文献
12.
Recent decades have revealed that many bacterial species are capable of communicating with each other, and this observation
has been largely responsible for a paradigm shift in microbiology. Whereas it was previously believed that bacteria lived
as individual cells, it is now acknowledged that bacteria preferentially live in communities in the form of primitive organisms
in which the behavior of individual cells is coordinated by cell–cell communication, known as quorum sensing (QS). Bacteria
use QS for regulation of the processes involved in their interaction with each other, their environment, and, particularly,
higher organisms We have focused on Pseudomonas aeruginosa, an opportunistic pathogen producing more than 30 QS-regulated virulence factors. P. aeruginosa causes several types of nosocomial infection, and lung infection in cystic fibrosis (CF) patients. We review the role of
QS in the protective mechanisms of P. aeruginosa and show how disruption of the QS can be used as an approach to control this cunning aggressor. 相似文献
13.
Ahmad J. Almalki Tarek S. Ibrahim Ehab S. Taher Mamdouh F. A. Mohamed Mahmoud Youns Wael A. H. Hegazy Amany M. M. Al-Mahmoudy 《Molecules (Basel, Switzerland)》2022,27(3)
Since the synthesis of prontosil the first prodrug shares their chemical moiety, sulfonamides exhibit diverse modes of actions to serve as antimicrobials, diuretics, antidiabetics, and other clinical applications. This inspiring chemical nucleus has promoted several research groups to investigate the synthesis of new members exploring new clinical applications. In this study, a novel series of 5(4H)-oxazolone-based-sulfonamides (OBS) 9a–k were synthesized, and their antibacterial and antifungal activities were evaluated against a wide range of Gram-positive and -negative bacteria and fungi. Most of the tested compounds exhibited promising antibacterial activity against both Gram-positive and -negative bacteria particularly OBS 9b and 9f. Meanwhile, compound 9h showed the most potent antifungal activity. Moreover, the OBS 9a, 9b, and 9f that inhibited the bacterial growth at the lowest concentrations were subjected to further evaluation for their anti-virulence activities against Pseudomonas aeruginosa and Staphylococcus aureus. Interestingly, the three tested compounds reduced the biofilm formation and diminished the production of virulence factors in both P. aeruginosa and S. aureus. Bacteria use a signaling system, quorum sensing (QS), to regulate their virulence. In this context, in silico study has been conducted to assess the ability of OBS to compete with the QS receptors. The tested OBS showed marked ability to bind and hinder QS receptors, indicating that anti-virulence activities of OBS could be due to blocking QS, the system that controls the bacterial virulence. Furthermore, anticancer activity has been further performed for such derivatives. The OBS compounds showed variable anti-tumor activities, specifically 9a, 9b, 9f and 9k, against different cancer lines. Conclusively, the OBS compounds can serve as antimicrobials, anti-virulence and anti-tumor agents. 相似文献
14.
Alex Yashkin Josep Rayo Larson Grimm Martin Welch Michael M. Meijler 《Chemical science》2021,12(12):4570
In recent years, the world has seen a troubling increase in antibiotic resistance among bacterial pathogens. In order to provide alternative strategies to combat bacterial infections, it is crucial deepen our understanding into the mechanisms that pathogens use to thrive in complex environments. Most bacteria use sophisticated chemical communication systems to sense their population density and coordinate gene expression in a collective manner, a process that is termed “quorum sensing” (QS). The human pathogen Pseudomonas aeruginosa uses several small molecules to regulate QS, and one of them is N-butyryl-l-homoserine lactone (C4-HSL). Using an activity-based protein profiling (ABPP) strategy, we designed biomimetic probes with a photoreactive group and a ‘click’ tag as an analytical handle. Using these probes, we have identified previously uncharacterized proteins that are part of the P. aeruginosa QS network, and we uncovered an additional role for this natural autoinducer in the virulence regulon of P. aeruginosa, through its interaction with PhzB1/2 that results in inhibition of pyocyanin production.Short-chain reactive probes can be used as tools to shed new light on virulence mechanisms in bacterial pathogens. 相似文献
15.
Recent progress in the chemistry and chemical biology of microbial signaling molecules: quorum-sensing pheromones and microbial hormones 总被引:1,自引:0,他引:1
Communication among microorganisms is mediated by secretion and detection of microbial signaling molecules such as quorum-sensing pheromones and microbial hormones. The molecules elicit the regulation of important genes necessary for microbial survival and often play important roles in interspecies or even inter-kingdom communication. Recent progress in the study of the signaling molecules has enabled us to eavesdrop on microbial conversations to gain insight on their intercellular communication system. This review summarizes the recent advances in the chemistry and chemical biology of these important microbial signaling molecules: acyl-homoserine lactones (AHLs), AI-2, CAI-1 related α-hydroxy ketones (AHKs), ComX pheromones, diffusible signal factors (DSFs), diffusible extracellular factor (DF), and Phytophthora mating hormones. 相似文献
16.
Three naturally occurring pyranosyl-like polyhalogenated metabolites 1-3 as well as their likely biogenetic precursor, the linear compound 4, have been isolated from the red alga Ptilonia magellanica. They are the first compounds within the genus that incorporate chlorine in their network. Compound 3 have structural features reminiscent of the universal chemical signal AI-2 (autoinducer-2) for bacterial communication. 相似文献
17.
18.
《印度化学会志》2023,100(9):101082
The emergence of bacterial resistance against chemical treatment is a big threat to the efficacy of bacterial infection treatment. One of the major reasons for resistance to antimicrobial agents is growth of microorganisms in biofilm. An alternative treatment by developing novel anti-biofilm agents had led to the concept of quorum sensing (QS) inhibition, which primarily targets QS signaling system by disrupting cell-cell communication. Therefore, this study focuses to develop novel antimicrobial agents which work by QS inhibition and act as anti-biofilm agents against Bacillus Subtilis and Pseudomonas Aeruginosa. In this work, a natural product-like scaffolds from Asinex library were screened and N-pyridin-2-yl-benzamide moiety was chosen to design and synthesize. Synthesized compounds were evaluated for potential anti-biofilm activity for the aforesaid microorganisms and also checked for cell viability assay, where two potent compounds 3a and 3c showed their static biofilm activity to ∼59% and ∼58% at 100 μM, respectively against Bacillus subtilis. These synthesized compounds were investigated for physicochemical parameters and binding mode prediction through molecular modelling tools. The interactions and stability of these compounds showed better affinity towards TasA and LasR proteins from Bacillus subtilis and Pseudomonas aeruginosa, respectively. Furthermore, molecular dynamic simulation for 100 ns was executed in order to appreciate the stability of the protein and ligand complex. The overall results promised that N-pyridin-2-yl-benzamide derivatives can be discovered as a lead in developing potent anti-quorum sensing agents against various bacteria. 相似文献
19.
Dittu Suresh Shekh Sabir Tsz Tin Yu Daniel Wenholz Theerthankar Das David StC. Black Naresh Kumar 《Molecules (Basel, Switzerland)》2021,26(12)
Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of Pseudomonas aeruginosa. Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, 8b and 8d, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin. 相似文献
20.
Victor Markus Orr Share Kerem Teral Nazmi Ozer Robert S. Marks Ariel Kushmaro Karina Golberg 《Molecules (Basel, Switzerland)》2020,25(22)
Governments are creating regulations for consumers to reduce their sugar intake, prompting companies to increase the ratio of artificial sweeteners in their products. However, there is evidence of some deleterious effects ascribed to the aforementioned synthetic agents and therefore consumers and food manufacturers have turned their attention to natural dietary sweeteners, such as stevia, to meet their sweetening needs. Stevia is generally considered safe; however, emerging scientific evidence has implicated the agent in gut microbial imbalance. In general, regulation of microbial behavior is known to depend highly on signaling molecules via quorum sensing (QS) pathways. This is also true for the gut microbial community. We, therefore, evaluated the possible role of these stevia-based natural sweeteners on this bacterial communication pathway. The use of a commercial stevia herbal supplement resulted in an inhibitory effect on bacterial communication, with no observable bactericidal effect. Purified stevia extracts, including stevioside, rebaudioside A (Reb A), and steviol revealed a molecular interaction, and possible interruption of Gram-negative bacterial communication, via either the LasR or RhlR receptor. Our in-silico analyses suggest a competitive-type inhibitory role for steviol, while Reb A and stevioside are likely to inhibit LasR-mediated QS in a non-competitive manner. These results suggest the need for further safety studies on the agents. 相似文献