Novel Alkyl Thioether Cyclodextrin Derivatives Against Bacterial Quorum Sensing in Aliivibrio fischeri (original) (raw)
Related papers
Marine Drugs, 2017
Marine natural products with antibiotic activity have been a rich source of drug discovery; however, the emergence of antibiotic-resistant bacterial strains has turned attention towards the discovery of alternative innovative strategies to combat pathogens. In many pathogenic bacteria, the expression of virulence factors is under the regulation of quorum sensing (QS). QS inhibitors (QSIs) present a promising alternative or potential synergistic treatment since they disrupt the signaling pathway used for intra-and interspecies coordination of expression of virulence factors. This review covers the set of molecules showing QSI activity that were isolated from marine organisms, including plants (algae), animals (sponges, cnidarians, and bryozoans), and microorganisms (bacteria, fungi, and cyanobacteria). The compounds found and the methods used for their isolation are the emphasis of this review.
World Journal of Microbiology and Biotechnology, 2013
Triclosan (TCS), an antimicrobial agent widely used in consumer and medical products, was complexed with 2-hydroxypropyl-b-cyclodextrin (HPbCD) and methyl-b-cyclodextrin (MbCD). Phase-solubility studies indicated that inclusion complexes of 1:1 stoichiometry were formed and allowed estimation of the associated equilibrium constants and free-energy changes. At the highest cyclodextrin concentrations investigated, an almost 20-fold increase in the apparent water solubility of TCS was determined. Susceptibility tests against Escherichia coli and Staphylococcus aureus showed that the TCS-HPbCD and TCS-MbCD complexes exhibited antibacterial properties higher than those of uncomplexed TCS. The two complexes were also found capable of interfering with cell-to-cell communication mechanisms in the C. violaceum model system relying on N-acylhomoserine lactone autoinducers. The inhibitory activity of TCS increased significantly upon inclusion of the drug in HPbCD or MbCD, with small differences between the two CDs. The results obtained suggest that the investigated complexes could be used for treating infections caused by TCS-susceptible pathogens or for preventing biofilm formation on indwelling medical devices such as catheters, stents and orthopedic implants.
Novel Linear Polymers Able to Inhibit Bacterial Quorum Sensing
Macromolecular Bioscience, 2015
Bacterial phenotypes such as biofilm formation, antibiotic resistance, virulence expression are associated with Quorum Sensing (QS). QS is a density-dependent regulatory system of gene expression controlled by specific signal molecules, such as Nacyl homoserine lactones (AHLs), produced and released by bacteria. This study reports the development of linear polymers capable to attenuate QS by adsorption of AHLs. Linear polymers were synthesized using methyl methacrylate as backbone monomer and methacrylic acid and itaconic acid as functional monomers. Two different QS-controlled phenotypes, Vibrio fischeri bioluminescence and Aeromonas hydrophila biofilm formation, were evaluated to test the polymers' efficiency. Results showed that both phenotypes were significantly affected by the polymers, with the itaconic acid-containing material more effective than the methacrylic acid one. The polymer inhibitory effects were reverted by addition of lactones, confirming attenuation of QS through sequestration of signal molecules. The polymers also showed no cytotoxicity when tested using a mammalian cell line.
Bacterial quorum sensing: functional features and potential applications in biotechnology
Journal of molecular microbiology and biotechnology, 2012
Quorum sensing (QS) represents an exceptional pattern of cell-to-cell communication in bacteria using self-synthesized signalling molecules known as autoinducers. Various features regulated by QS in bacteria include virulence, biofilm formation, sporulation, genetic competence and bioluminescence, among others. Other than the diverse signalling properties of autoinducers, there are non-signalling properties also associated with these signalling molecules which make them potential antimicrobial agents and metal chelators. Additionally, QS signal antagonism has also been shown to be a promising alternative for blocking pathogenic diseases. Besides, QS has impressive design features useful in tissue engineering and biosensor technology. Although many aspects of QS are well understood, several other features remain largely unknown, especially in biotechnology applications. This review focuses on the functional features and potential applications of QS signalling molecules in biotechnology.
Bioorganic Chemistry, 2017
Quorum sensing (QS) is a cell-to-cell signaling communication system that controls the virulence behavior of a broad spectrum of bacterial pathogens, participating also in the development of biofilms, responsible of the antibiotic ineffectiveness in many infections. Therefore, QS system is an attractive target for antimicrobial therapy. In this study, we compare the effect of seven structurally related coumarins against bacterial growth, biofilm formation and elastase activity of Pseudomonas aeruginosa. In addition, the anti-pathogenic capacity of the seven coumarins was evaluated on the wild type and the biosensor strain of Chromobacterium violaceum. The comparative study of coumarins showed that molecules with hydroxyl groups on the aromatic ring displayed higher activity on the inhibition of biofilm formation of P. aeruginosa over coumarins with substituents in positions 3 and 4 or without the double 3,4-bond. These 3 or 4-hydroxylated positions caused a decrease in the anti-biofilm activity obtained for coumarin. However, the hydroxyl group in position 3 of the pyrone ring was important for the inhibition of C. violaceum QS and elastolytic activity of P. aeruginosa. The effects observed were active independently of any effect on growth. According to our results, coumarin and its hydroxylated derivatives represent an interesting group of compounds to use as anti-virulence agents against the human pathogen P. aeruginosa.
Journal of the American Chemical Society, 1993
a-, j3-, and y-cyclodextrin derivatives bearing a p(dimethy1amino)benzoyl (DMAB) moiety (DMAB-aCyD, DMAB-BCyD, and DMAB-yCyD, respectively) have been synthesized as fluorescent sensors of molecular recognition. These compounds show dual fluorescence emission arising from normal planar (NP) and twisted intramolecular charge transfer (TICT) exited states, and among them strong TICT emission was observed for DMAB-j3CyD. The induced circular dichroism spectra of the derivatives suggest that only DMAB-j3CyD among other derivatives binds the DMAB moiety into its own cavity, forming an intramolecular inclusion complex. This conformation was confirmed by the analysis of its 1H-NMR data and was related to its strong TICT emission. The intensity of the TICT emission of DMAB-j3CyD decreased markedly with increasing the concentration of cyclic alchols, monoterpenes, or steroids. This observation was explained by the guest-induced location change of the DMAB moiety from inside to outside of the cavity. Since the TICT emission intensity depended on the size, shape, and polarity of the guest molecules, DMAB-j3CyD was useful as a fluorescent chemosensor of molecular recognition. Fluorescent sensors and chromogenic indicators that transform binding of molecules into spectroscopic signals are current interest.' However, only few sensing mechanisms have been described.2 Cyclodextrins (CyDs) are series of cyclic oligosaccharides composed of six or more D-glucopyranose units. The six, seven, and eight D-glucopyranosemembers of CyDs are named as a-, Band nd yCyD, respectively, each having an approximate internal diameter of 5.7, 7.8, and 9.5 They have attracted great interest because of their abilities to bind various organic compounds into their cavities in aqueous solution. On this basis, modified CyDs with appropriate functionalgroups act as enzymemimic catalysts or receptor^.^ For the purpose of constructing CyD-based sensors, native CyD must be modified by chromophores, because CyDs themselves are spectroscopically inert. Ueno et al. prepared several chromophore-modified CyDs and observed that they act as sensors or indicators of molecule^.^ Pyrene-modified CyDs, for example, act as fluorescent chemosensow, changing the excimer emission intensities upon guest binding.5a*b-g We now report novel fluorescent sensors that detect various organic compounds by twisted intramolecular charge transfer (TICT) fluorescence.6 In many of the CyD-based sensors, the location change of the chromophore which is attached to CyD from inside to outside of the CyD cavities upon guest binding results in a drastic
Synthetic Polymers for Simultaneous Bacterial Sequestration and Quorum Sense Interference
Angewandte Chemie International Edition, 2011
Materials that interfere with bacteria-host interactions are an attractive approach for controlling infectious diseases . Synthetic polymers are especially useful in this context, because their affinity with cell surface receptors can be tailored through multivalent ligand display, while at the same time avoiding selection pressure and resistance invoked in bacteria by antibiotics. However, many bacterial species employ additional strategies for environmental adaptation and host invasion, thus confounding therapies that depend on cell sequestration alone. Amongst these mechanisms are communication systems such as quorum sensing (QS), which allows bacteria to synchronize transcriptional changes at the population level a, route 2). Inhibition of QS is itself a potential further method of controlling bacterial infection, but targeting QS signals in isolation can still allow bacterial infection by alternative pathways. Materials that could interfere with both communication mechanisms and cell adhesion/aggregation at the same time would allow greater flexibility in anti-infective strategies. Herein, we report polymers that combine potent activity in binding QS autoinducers with effective adhesion at bacterial surfaces ( .
Quorum Sensing Inhibition by Marine Bacteria
Marine Drugs
Antibiotic resistance has been increasingly reported for a wide variety of bacteria of clinical significance. This widespread problem constitutes one of the greatest challenges of the twenty-first century. Faced with this issue, clinicians and researchers have been persuaded to design novel strategies in order to try to control pathogenic bacteria. Therefore, the discovery and elucidation of the mechanisms underlying bacterial pathogenesis and intercellular communication have opened new perspectives for the development of alternative approaches. Antipathogenic and/or antivirulence therapies based on the interruption of quorum sensing pathways are one of several such promising strategies aimed at disarming rather than at eradicating bacterial pathogens during the course of colonization and infection. This review describes mechanisms of bacterial communication involved in biofilm formation. An overview of the potential of marine bacteria and their bioactive components as QS inhibitors...
Anti-quorum sensing agents: a potential alternative for antibiotics
International Journal of Agricultural and Applied Sciences
Quorum sensing (QS) is a bacterial cell to cell communication, which helps bacteria to mount population-density-dependent infection to overcome the defence responses from host. In this mechanism some diffusible chemical signalling compounds are involved, known as autoinducers, which are directly proportional to the population cell density. The main role of QS is to coordinate the expression of several collective traits, including the production of virulence factors, secondary metabolites with antimicrobial activity, pigment production, siderophore production, epiphytic fitness, bioluminescence, plasmid transfer, motility and biofilm formation. Due to the growing bacterial resistance to the antibiotics that have been overused, it has become necessary to search for alternative antimicrobial therapies. One of them is anti-quorum sensing agents/anti-biofilm agents/quorum sensing inhibitors that disrupts the bacterial communication. This study discusses the various QS-disrupting mechanis...