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1.
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
2.
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
3.
4.
Bacteria communicate among themselves using certain chemical signaling molecules. These signaling molecules generally are
N-acyl homoserine lactones (AHLs) in Gram-negative bacteria and oligopeptides in Gram-positive bacteria. In addition, both
Gram-positive and Gram-negative bacteria produce a family of signaling molecules known as autoinducer-2 that they employ for
their communications. Bacteria coordinate their behavior by releasing and responding to the chemical signaling molecules present
in proportion to their population density. This phenomenon is known as quorum sensing. The role of bacteria in the pathogenesis
of several diseases, including gastrointestinal (GI) disorders, is well established. Moreover, rather recently bacterial quorum
sensing has been implicated in the onset of bacterial pathogenicity. Thus, we hypothesized that the signaling molecules involved
in bacterial communication may serve as potential biomarkers for the diagnosis and management of several bacteria-related
diseases. For that, we previously developed a method based on genetically engineered whole-cell sensing systems for the rapid,
sensitive, cost-effective and quantitative detection of AHLs in biological samples, such as saliva and stool, from both healthy
and diseased individuals with GI disorders. Although various analytical methods, based on physical-chemical techniques and
bacterial whole-cell biosensors, have been developed for the detection of AHLs in the supernatants of bacterial cultures,
only a few of them have been applied to AHL monitoring in real samples. In this paper, we report work performed in our laboratory
and review that from others that describes the detection of AHLs in biological, clinical samples, and report some of our recent
experimental results. 相似文献
5.
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
6.
James T. HodgkinsonWarren R.J.D. Galloway Mariangela CasoliHarriet Keane Xianbin SuGeorge P.C. Salmond Martin WelchDavid R. Spring 《Tetrahedron letters》2011,52(26):3291-3294
The ready availability of native quorum sensing molecules and related structural analogues is of significant biological interest in the development of methods to manipulate bacterial quorum sensing systems in a useful fashion. In this Letter we report robust routes for the synthesis of a range of N-acylated-l-homoserine lactone (AHL) quorum sensing molecules. Crucially, we have analysed the enantiopurity of the final AHLs and in all cases, excellent levels were observed. 相似文献
7.
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
8.
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
9.
Antibody interference with N-acyl homoserine lactone-mediated bacterial quorum sensing 总被引:2,自引:0,他引:2
Kaufmann GF Sartorio R Lee SH Mee JM Altobell LJ Kujawa DP Jeffries E Clapham B Meijler MM Janda KD 《Journal of the American Chemical Society》2006,128(9):2802-2803
Many bacterial pathogens coordinate their virulence factor expression in a cell density-dependent manner. This population-dependent coordination of gene expression in bacteria has been termed "quorum sensing" (QS). N-Acyl homoserine lactones (AHLs) are used by over 70 Gram-negative bacterial species as autoinducers. Inhibition of QS signaling might represent a new target for antimicrobial therapy. Here we report the hapten design, synthesis, generation of monoclonal antibodies (mAbs) against AHLs, and the evaluation of these mAbs for their ability to blunt QS signaling and inhibit virulence factor expression in P. aeruginosa. The mAbs can be envisioned as a tool for future investigations into AHL-based QS, which may aid in gaining new insights into the pathogenesis of P. aeruginosa and may ultimately lead to the development of new strategies to combat bacterial diseases. 相似文献
10.
Dr. Meng Gao Dr. Bolong Xu Dr. Yang Huang Jiayu Cao Lili Yang Dr. Xi Liu Alisher Djumaev Di Wu Moxichexra Shoxiddinova Xiaoming Cai Behruz Tojiyev Dr. Huizhen Zheng Prof. Xuehua Li Prof. Kunduz Normurodova Prof. Huiyu Liu Prof. Ruibin Li 《Angewandte Chemie (International ed. in English)》2023,62(27):e202305485
Biofilm formation is a major threat to industry, the environment and human health. While killing of embedded microbes in biofilms may inevitably lead to the evolution of antimicrobial resistance (AMR), catalytic quenching of bacterial communications by lactonase is a promising antifouling approach. Given the shortcomings of protein enzymes, it is attractive to engineer synthetic materials to mimic the activity of lactonase. Herein, an efficient lactonase-like Zn−Nx−C nanomaterial was synthesized by tuning the coordination environment around zinc atoms to mimic the active domain of lactonase for catalytical interception of bacterial communications in biofilm formation. The Zn−Nx−C material could selectively catalyze 77.5 % hydrolysis of N-acylated-L-homoserine lactone (AHL), a critical bacterial quorum sensing (QS) signal in biofilm construction. Consequently, AHL degradation downregulated the expression of QS-related genes in antibiotic resistant bacteria and significantly prevented biofilm formation. As a proof of concept, Zn−Nx−C-coated iron plates prevented 80.3 % biofouling after a month exposure in river. Overall, our study provides a nano-enabled contactless antifouling insight to avoid AMR evolution by engineering nanomaterials for mimicking the key bacterial enzymes (e.g., lactonase) functioning in biofilm construction. 相似文献
11.
Quorum sensing (QS) regulates the production of virulence factors and the maturation of biofilms in many bacteria, including Pseudomonas aeruginosa. The QS cascade is activated by the interaction of bacterial signaling molecules, called autoinducers (AIs), with their corresponding regulatory proteins. Here, we report a series of studies to define the stereochemical preferences of synthetic agonists and perform docking studies to understand the microenvironment of the binding site in P. aeruginosa QS regulators. One of the key findings of this work is that the ring structure and the absolute and relative stereochemistries of the amide and hydroxyl groups dictate the agonist activity. This study aids in determining important structural and stereochemical characteristics necessary for interaction with the QS regulatory proteins, thus expanding our understanding of their inducer binding sites. 相似文献
12.
Ortori CA Dubern JF Chhabra SR Cámara M Hardie K Williams P Barrett DA 《Analytical and bioanalytical chemistry》2011,399(2):839-850
An LC-MS/MS method, using positive mode electrospray ionization, for the simultaneous, quantitative and targeted profiling of the N-acyl-L-homoserine lactone (AHL) and 2-alkyl 4-(1H)-quinolone (AQ) families of bacterial quorum-sensing signaling molecules (QSSMs) is presented. This LC-MS/MS technique was applied to determine the relative molar ratios of AHLs and AQs produced by Pseudomonas aeruginosa and the consequences of mutating individual or multiple QSSM synthase genes (lasI, rhlI, pqsA) on AHL and AQ profiles and concentrations. The AHL profile of P. aeruginosa was dominated by N-butanoyl-L-homoserine lactone (C4-HSL) with lesser concentrations of N-hexanoyl-L-homoserine lactone (C6-HSL) and 3-oxo-substituted longer chain AHLs including N-(3-oxodecanoyl)-L-homoserine lactone (3-oxo-C10-HSL) and N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL). The AQ profile of P. aeruginosa comprised the C7 and C9 long alkyl chain AQs including 2-heptyl-4-hydroxyquinoline (HHQ), 2-nonyl-4-hydroxyquinoline, the "pseudomonas quinolone signal" (2-heptyl-3-hydroxy-4-quinolone) and the N-oxides, 2-heptyl-4-hydroxyquinoline N-oxide and 2-nonyl-4-hydroxyquinoline N-oxide. Application of the method showed significant effects of growth medium type on the ratio and the nature of the QSSMs synthesized and the dramatic effect of single, double and triple mutations in the P. aeruginosa QS synthase genes. The LC-MS/MS methodology is applicable in organisms where either or both AHL and AQ QSSMs are produced and can provide comprehensive profiles and concentrations from a single sample. 相似文献
13.
Expanding dialogues: from natural autoinducers to non-natural analogues that modulate quorum sensing in Gram-negative bacteria 总被引:1,自引:0,他引:1
Bacteria are capable of "communicating" their local population densities via a process termed quorum sensing (QS). Gram-negative bacteria use N-acylated l-homoserine lactones (AHLs), in conjunction with their cognate LuxR-type receptors, as their primary signalling circuit for QS. In this critical review, we examine AHL signalling in Gram-negative bacteria with a primary focus on the design of non-natural AHLs, their structure-activity relationships, and their application in chemical biological approaches to study QS (72 references). 相似文献
14.
Jaramillo-Colorado B Olivero-Verbel J Stashenko EE Wagner-Döbler I Kunze B 《Natural product research》2012,26(12):1075-1086
Essential oils from Colombian plants were characterised by GC-MS, and assayed for anti-quorum sensing activity in bacteria sensor strains. Two major chemotypes were found for Lippia alba, the limonene-carvone and the citral (geranial-neral). For other species, the main components included α-pinene (Ocotea sp.), β-pinene (Swinglea glutinosa), cineol (Elettaria cardamomun), α-zingiberene (Zingiber officinale) and pulegone (Minthostachys mollis). Several essential oils presented promising inhibitory properties for the short chain AHL quorum sensing (QS) system, in Escherichia coli containing the biosensor plasmid pJBA132, in particular Lippia alba. Moderate activity as anti-QS using the same plasmid, were also found for selected constituents of essential oils studied here, such as citral, carvone and α-pinene, although solely at the highest tested concentration (250?μg?mL(-1)). Only citral presented some activity for the long chain AHL QS system, in Pseudomonas putida containing the plasmid pRK-C12. In short, essential oils from Colombian flora have promising properties as QS modulators. 相似文献
15.
J. P. Van der Berg W. A. Velema W. Szymanski A. J. M. Driessen B. L. Feringa 《Chemical science》2015,6(6):3593-3598
Bacteria use a communication system, called quorum sensing (QS), to organize into communities and synchronize gene expression to promote virulence and secure survival. Here we report on a proof-of-principle for externally interfering with this bacterial communication system, using light. By employing photoswitchable small molecules, we were able to photocontrol the QS-related bioluminescence in an Escherichia coli reporter strain, and the expression of target QS genes and pyocyanin production in Pseudomonas aeruginosa. 相似文献
16.
Homogentisic acid γ-lactone exhibited excellent anti-quorum sensing (QS) and anti-biofilm activities against Pseudomonas aeruginosa. Moreover, it suppressed the QS-dependent virulence factors in P. aeruginosa by quenching its QS signal molecules. 相似文献
17.
Lowery CA Park J Kaufmann GF Janda KD 《Journal of the American Chemical Society》2008,130(29):9200-9201
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. The AI-2-based QS system represents the most studied of these proposed interspecies systems, and has been proposed to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the treatment of bacterial infections and the study of unknown AI-2-based QS systems. Toward this end, we have designed and synthesized a panel of 4,5-dihydroxy-2,3-pentanedione/AI-2 analogues and evaluated their effects on the AI-2 QS of various bacteria. The panel of compounds exhibited differential effects in the bacterial cell lines examined, providing a platform for the development of broad-spectrum modulators of AI-2-based QS. 相似文献
18.
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
19.
Dr. Vitaly V. Komnatnyy Dr. Wen‐Chi Chiang Prof. Dr. Tim Tolker‐Nielsen Prof. Dr. Michael Givskov Prof. Dr. Thomas E. Nielsen 《Angewandte Chemie (International ed. in English)》2014,53(2):439-441
Medical devices employed in healthcare practice are often susceptible to microbial contamination. Pathogenic bacteria may attach themselves to device surfaces of catheters or implants by formation of chemically complex biofilms, which may be the direct cause of device failure. Extracellular bacterial lipases are particularly abundant at sites of infection. Herein it is shown how active or proactive compounds attached to polymeric surfaces using lipase‐sensitive linkages, such as fatty acid esters or anhydrides, may be released in response to infection. Proof‐of‐concept of the responsive material is demonstrated by the bacteria‐triggered release of antibiotics to control bacterial populations and signaling molecules to modulate quorum sensing. The self‐regulating system provides the basis for the development of device‐relevant polymeric materials, which only release antibiotics in dependency of the titer of bacteria surrounding the medical device. 相似文献