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Redox-active molecules used for the electrochemical analysis of QS. A. Pyocyanin used by Bukelman et al. 97 and Sharp et al. 98 B. PQS used by Zhou et al. 99 C. p-Aminophenol (PAP) used by Baldrich et al. 100
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Bacteria frequently manifest distinct phenotypes as a function of cell density in a phenomenon known as quorum sensing (QS). This intercellular signalling process is mediated by "chemical languages" comprised of low-molecular weight signals, known as autoinducers, and their cognate receptor proteins. As many of the phenotypes regulated by QS can ha...
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... Fungal phytotoxin sphaeropsidin A was able to inhibit the biofilm of clinical MRSA at a concentration of 1.56 μg/ml [44]. S. aureus pathogenesis and biofilm formation is regulated by cell-to-cell communication using quorum sensing [45,46]. Though treatment of MRSA is a hard task as it get multidrug resistance, therefore the best method for treating a biofilm-related infection is by preventing initial infection altogether. ...
There is an urgent call to search for novel natural compounds against developing multidrug‐resistant microorganisms. The present work focuses on the characterization of a plant‐associated fungus having bioactivity against methicillin‐resistant Staphylococcus aureus (MRSA) strains. A fungal strain P31 was isolated from bark of Dillenia pentagyna and identified as Pestalotiopsis microspora. The maximum anti‐MRSA activity was observed from extract of P31 grown in sabouraud dextrose broth. The minimum inhibitory concentrations (MIC) values of P31 extract were 14 μg/ml for methicillin‐sensitive S. aureus (MSSA) and 32 μg/ml for MRSA strain, respectively. A crude P31 extract showed strong bactericidal activity by killing all treated MRSA cells within 24 h of treatment at their respective MIC value. A scanning electron microscopic study visualized morphological damage of MRSA cells. The membrane permeability of P31 extract‐treated MRSA cells gradually increased which caused release of internal cytoplasmic nucleic acids, proteins and potassium ions (K+) from cells suggesting cell lysis or leakage from cells. A very low concentration of P31 extract was able to inhibit biofilm formed by MRSA cells. Thin layer chromatographic separation followed by gas chromatography‐mass spectrometry analysis of the P31 extract revealed a number of antimicrobial compounds along with an anti‐MRSA compound 2,4‐di‐tert‐butylphenol. In addition, the P31 extract also showed in‐vitro human blood clot lysis activity at various concentrations. The clot lysis activity of P31 extract was found maximum at 500 µg/ml. These findings suggest that fungal isolate P31 has potential as a source of anti‐MRSA compounds useful in staph infections.
... While there are a number of critical phenotypes regulated by QS within the heterogenous environment of the rhizosphere, the density of bacteria required and the frequency with which these events occur remain ill-defined. The number of cells required for QS to occur within a particular environment is highly variable and critically dependent on both biotic and abiotic factors (Praneenararat et al. 2012;Sifri 2008). Biological considerations include: (1) the rates of AI production and release into the environment, (2) the distance between participating cells, and (3) the concentration at which the AI associates with its cognate receptor. ...
Plant-fungal symbioses are of great importance to agriculture. Phytopathogenic fungi, which cause disease in plants as they consume host tissues, are a major threat to global food security. Conversely, endophytes and mycorrhizal fungi, which can engage in mutually beneficial relationships with host plants, are capable of promoting plant health, growth, and development. Such plant-fungal symbioses, whether they be harmful or beneficial to host plants, require complex and continuous molecular cross talk, including the secretion of fungal effector proteins into the plant apoplast and cytoplasm. Fungal effectors are broadly defined as proteins which modulate plant physiology in ways which facilitate fungal colonization and growth within the host plant. These proteins typically share three common features: (1) an amino(N)-terminal signal peptide to allow for secretion, (2) high cysteine content that facilitates structural stability, and (3) small molecular mass (typically ≤30 kDa). However, fungi often possess a large number of genes which fit these criteria—only a subset of which truly act as effector proteins. Progress in identifying effector proteins has been hindered by the fact that most apparently do not share significant sequence similarities with effectors of other genera. This is thought to be an adaptive trait within the context of the co-evolutionary arms race between plant-associated fungi and their host plants, in which plants are continually evolving novel variations in their resistance (R) proteins to allow for improved detection of fungal effector proteins, while fungi diversify their effectors to evade detection. Despite this fact, there are a limited number of domains and motifs which have been found in effector proteins from a variety of plant-associated fungi. Some of these conserved sequence features, such as CFEM and LysM domains, are shared among effector proteins of phytopathogenic and mutualistic fungi, while others may be tailored to the unique lifestyles of individual species or genera. Relying upon the common features and few conserved motifs and domains, in silico tools are often relied upon to mine fungal genomes for candidate effector proteins. Although this process is valuable in curating lists of potential effectors, experimental validation of effector status is still required. To that end, many studies have utilized knockout or overexpression of putative effector protein-coding genes in order to elucidate the importance of putative effectors in the establishment and maintenance of fungal-plant symbioses—a method which is susceptible to issues of gene redundancy. The vast majority of literature on fungal effectors has focused on fungal pathogens of above-ground plant tissue; however this chapter also emphasizes the limited state of understanding on effector proteins from rhizospheric fungi.KeywordsMetarhiziumEndophyteEffector proteinsPlant symbiosis
... While there are a number of critical phenotypes regulated by QS within the heterogenous environment of the rhizosphere, the density of bacteria required and the frequency with which these events occur remain ill-defined. The number of cells required for QS to occur within a particular environment is highly variable and critically dependent on both biotic and abiotic factors (Praneenararat et al. 2012;Sifri 2008). Biological considerations include: (1) the rates of AI production and release into the environment, (2) the distance between participating cells, and (3) the concentration at which the AI associates with its cognate receptor. ...
The rhizosphere is a biologically and chemically rich and diverse environment that arises through the interplay between host plant and the microorganisms that inhabit this space. The diverse microorganisms which call this region home are crucial players in determining the success and failure of the scaffold (i.e., host plant) they inhabit. Rhizosphere interactions can impact agricultural yields, disease resistance, nutrient utilization, nutrient uptake, ecological robustness, and secondary metabolite production. How this mixture of cues and signals directs the actions of potentially deleterious or beneficial microbial associations with host plants is crucial to improving agricultural yields, food safety, and our general understanding of terrestrial ecology. Frequently, symbiotic microorganisms (both pathogenic and mutualistic) within the rhizosphere tightly regulate phenotypic switching to behaviors that are relevant to their host plants based on population density, a phenomenon known as quorum sensing (QS). QS has emerged as a crucial regulatory strategy for rhizosphere behaviors such as nitrogen fixation, as well as biofilm and virulence factor production. Here we review a variety of known QS mechanisms, how biotic and abiotic factors influence QS size and persistence, the effectiveness of QS at the root surface, and provide relevant examples of QS microorganisms within the rhizosphere. We also explore how host plants have evolved to detect and respond to QS signals, as well as the potential significance of this discovery. Finally, we consider how to integrate QS processes into existing models for biotic and abiotic cycles also present at the rhizosphere.KeywordsRhizosphereQuorum sensingN-Acyl-l-homoserine lactonesAHLs
... За последние годы было идентифицировано боль шое количество молекул природного и синтетического происхождения, а также ферменты и АТ, подавляющие QS. Эти соединения действуют на различные звенья си стемы регуляции QS по разным механизмам, среди ко торых инактивация рецепторов QS, ингибирование син теза аутоиндукторов, их ферментативная деградация или связывание АТ [31][32][33][34]. ...
The most important goal of medical microbiology in terms of treating infectious diseases nowadays and in the coming decades will be the development of antibacterial agents that are effective against resistant pathogens and reduce the selection of antimicrobial resistance. In this regard, along with the search for new classic antibiotics, it is necessary to develop alternative strategies. Virulence factors that determine the key stages of the infection process, both acute and chronic, including adhesins, toxins, bacterial quorum sensing, secretory systems, could be potential targets. The strategy for the development of antivirulence drugs is already showing its potential in the treatment of nosocomial, complicated and chronic infections as part of complex therapy and for prevention. The review presents the results of studies of drugs that have already shown efficacy in model infections in animals or have either passed to the stage of clinical trials or have already been registered. The development of effective combination therapy regimens will minimize the risks of acquiring resistance.
... The antibody XYD-11G2 has also been revealed to mediate the breakdown of 3-oxo-C12-HSL signaling system, thereby preventing the synthesis of pyocyanin in Gram-negative bacteria. [54,55] Other studies have shown that the antibody AP4-24H11 can block the quorum sensing signaling system of Staphylococcus aureus and can remarkably reduce the tissue necrosis inside of the infected model. [56,57] ...
Quorum sensing is when a sufficient population of micro-organisms, such as bacteria, situated in a given environment can trigger a system of cell-cell communication in these micro-organisms. Researchers, increasingly, have shown that bacteria are unable to thrive independently as solitary cells, but as colonial organisms, communicating intercellularly, and enhancing their capacity to adapt to changing environmental conditions. To a great extent, researchers today have come to terms with the intricacies surrounding bacterial conversations, and responses/signals. Herein, the quorum sensing and its signaling in bacteria, from briefs about the mechanism, its discovery, and involved molecules, to its applications/uses has been tersely reviewed. Understanding bacteria quorum sensing mechanisms/processes can be very challenging. Several strategies employed to disrupt quorum sensing in bacteria have involved receptor inactivation, signaled synthesis inhibition including its degradation, blocking of quorum sensing using antibodies, as well as the combination of antibiotics and anti-quorum sensing agents. The future use of quorum sensing is hopeful, given the emerging applications like its use in biofouling reduction, biofuel production, biodegradation as well as winemaking.
... [3] Apart from the well-organized cell wall structures, the mycobacterialb iofilm acts as ab arrier to adverse environmental stresses.B iofilm formation follows stages of 1) adhesion to a surface; 2) sessile cell division;3 )matrix biosynthesis, and 4) dispersal of the biofilm. [4] Intercellular signalingo ccurs during biofilm formation through quorum-sensingm olecules, such as autoinducing peptides, [5] and secondary messengers, such as cyclic diguanosine monophosphate. [6] The biofilm matrixi sc omposed of ah eterogeneous mixture of extracellular polymeric substances (EPSs), polysaccharides, glycopeptides, GPLs, extracellular DNA (e-DNA), proteins, lipids, and water. ...
Lipomannan and lipoarabinomannan are integral components of the mycobacterial cell wall. Earlier studies demonstrated that synthetic arabinan and arabinomannan glycolipids acted as inhibitors of mycobacterial growth, in addition to exhibiting inhibitory activities of mycobacterial biofilm. Herein, it is demonstrated that synthetic mannan glycolipids are better inhibitors of mycobacterial growth, whereas lipoarabinomannan has a higher inhibition efficiency to biofilm. Syntheses of mannan glycolipids with a graded number of mannan moieties and an arabinomannan glycolipid are conducted by chemical methods and subsequent mycobacterial growth and biofilm inhibition studies are conducted on Mycobacterium smegmatis. Growth inhibition of (73±3) % is observed with a mannose trisaccharide containing a glycolipid, whereas this glycolipid did not promote biofilm inhibition activity better than that of arabinomannan glycolipid. The antibiotic supplementation activities of glycolipids on growth and biofilm inhibitions are evaluated. Increases in growth and biofilm inhibitions are observed if the antibiotic is supplemented with glycolipids, which leads to a significant reduction of inhibition concentrations of the antibiotic.
... [116,117] In-vitro, [118] al. found in their study [100] that the antibody RS2-1G9 can bind to 3-oxo-C12-HSL in the extracellular environment of Pseudomonas aeruginosa, thereby attenuating the inflammatory response of the host. XYD-11G2 antibody has been shown to catalyze the hydrolysis of 3-oxo-C12-HSL signaling, thus inhibiting the pyocyanin production by Gram-negative bacteria [101,102]. The monoclonal antibody AP4-24H11 was found to block the QS signal of Gram-positive Staphylococcus aureus by interfering with AIP IV [103]. ...
Bacterial quorum sensing (QS) is a cell-to-cell communication in which specific signals are activated to coordinate pathogenic behaviors and help bacteria acclimatize to the disadvantages. The QS signals in the bacteria mainly consist of acyl-homoserine lactone, autoinducing peptide, and autoinducer-2. QS signaling activation and biofilm formation lead to the antimicrobial resistance of the pathogens, thus increasing the therapy difficulty of bacterial diseases. Anti-QS agents can abolish the QS signaling and prevent the biofilm formation, therefore reducing bacterial virulence without causing drug-resistant to the pathogens, suggesting that anti-QS agents are potential alternatives for antibiotics. This review focuses on the anti-QS agents and their mediated signals in the pathogens and conveys the potential of QS targeted therapy for bacterial diseases.
... The fundamentally chemical nature of QS systems makes the prospect of applying chemical tools to study these pathways particularly attractive (Praneenararat, Palmer and Blackwell 2012). Using chemical probes to perturb QS circuitry can offer several benefits over traditional genetic approaches. ...
... However, non-lactone QS inhibitors have also been discovered, with notable early examples being the halogenated furanones and derivatives thereof (Hentzer et al. 2002). For detailed information regarding the synthesis, screening and structure-activity relationships (SARs) of previously reported small molecule QS probes in Gram-negative bacteria, we direct the reader to the following comprehensive reviews (Mattmann and Blackwell 2010;Galloway et al. 2011Galloway et al. , 2012Praneenararat, Palmer and Blackwell 2012;O'Connell et al. 2013;Zhu and Kaufmann 2013;Rampioni, Leoni and Williams 2014). Because of the rapid evolution of the field, we will limit the discussion in this section to only the most recent (2011 onward) reports of small molecule QS modulators that (1) have clearly defined chemical structures, (2) possess noteworthy activities in reporter gene and/or phenotypic assays and (3) have been demonstrated (via reporter assays or in vitro experiments) to bind a target QS receptor or QS signal synthase. ...
Bacteria can utilize chemical signals to coordinate the expression of group-beneficial behaviors in a method of cell–cell communication called quorum sensing (QS). The discovery that QS controls the production of virulence factors and biofilm formation in many common pathogens has driven an explosion of research aimed at both deepening our fundamental understanding of these regulatory networks and developing chemical agents that can attenuate QS signaling. The inherently chemical nature of QS makes studying these pathways with small molecule tools a complementary approach to traditional microbiology techniques. Indeed, chemical tools are beginning to yield new insights into QS regulation and provide novel strategies to inhibit QS. Here, we review the most recent advances in the development of chemical probes of QS systems in Gram-negative bacteria, with an emphasis on the opportunistic pathogen Pseudomonas aeruginosa. We first describe reports of novel small molecule modulators of QS receptors and QS signal synthases. Next, in several case studies, we showcase how chemical tools have been deployed to reveal new knowledge of QS biology and outline lessons for how researchers might best target QS to combat bacterial virulence. To close, we detail the outstanding challenges in the field and suggest strategies to overcome these issues.
... Chemical methods to modulate QS in bacteria have attracted considerable interest over the past decade, due in part to the temporal and spatial control they can provide and their often ready applicability to biologically relevant environments (50)(51)(52). The development of chemical probes capable of modulating the S. epidermidis agr system could provide valuable tools for better understanding the role of the agr system in colonization and infection by this common bacterium. ...
Staphylococcus epidermidis is frequently implicated in human infections associated with indwelling medical devices due to its ubiquity in the skin flora and formation of robust biofilms. The accessory gene regulator (agr) quorum sensing (QS) system plays a prominent role in the establishment of biofilms and infection by this bacterium. Agr activation is mediated by the binding of a peptide signal (or autoinducing peptide, AIP) to its cognate AgrC receptor. Many questions remain about the role of QS in S. epidermidis infections, as well as in mixed-microbial populations on a host, and chemical modulators of its agr system could provide novel insights into this signaling network. The AIP ligand provides an initial scaffold for the development of such probes; however, the structure-activity relationships (SARs) for activation of S. epidermidis AgrC receptors by AIPs are largely unknown. Herein, we report the first SAR analyses of an S. epidermidis AIP by performing systematic alanine and D-amino acid scans of the S. epidermidis AIP-I. Based on these results, we designed and identified potent, pan-group inhibitors of the AgrC receptors in the three S. epidermidis agr groups, as well as a set of AIP-I analogs capable of selective AgrC inhibition in either specific S. epidermidis agr groups or in another common staphylococcal species, S. aureus. In addition, we uncovered a non-native peptide agonist of AgrC-I that can strongly inhibit S. epidermidis biofilm growth. Together, these synthetic analogs represent new and readily accessible probes for investigating the roles of QS in S. epidermidis colonization and infections.
... Indeed, the ability to modulate QS with nonnative molecules has tremendous implications for artificially disrupting or promoting both pathogenic and mutualistic behavior (Galloway et al., 2011Geske et al., 2008a). The spatial and temporal control afforded by chemical probes can enable a deeper understanding of important microbial phenotypes and possibly have direct therapeutic potential (Bjarnsholt and Givskov, 2007;Clatworthy et al., 2007;Praneenararat et al., 2012). As therapeutics, QS inhibitors have a prospective advantage over traditional antibiotic therapies, because recent sociomicrobiology studies suggest that resistance is likely to spread more slowly to QS inhibitors (that target virulence phenotypes) than to traditional antibiotics (that target growth; Gerdt and Blackwell, 2014;Mellbye and Schuster, 2011). ...
Gram-negative bacteria use N-acyl L-homoserine lactone (AHL) quorum-sensing (QS) signals to regulate the expression of myriad phenotypes. Non-native AHL analogs can strongly attenuate QS receptor activity and thereby QS signaling; however, we currently lack a molecular understanding of the mechanisms by which most of these compounds elicit their agonistic or antagonistic profiles. In this study, we investigated the origins of striking activity profile switches (i.e., receptor activator to inhibitor, and vice versa) observed upon alteration of the lactone head group in certain AHL analogs. Reporter gene assays of mutant versions of the Pseudomonas aeruginosa QS receptor LasR revealed that interactions between the ligands and Trp60, Tyr56, and Ser129 govern whether these ligands behave as LasR activators or inhibitors. Using this knowledge, we propose a model for the modulation of LasR by AHL analogs-encompassing a subtly different interaction with the binding pocket to a global change in LasR conformation.
