Resistance to quorum-quenching compounds. - Related Documents




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915601.0000Resistance to quorum-quenching compounds. Bacteria have the remarkable ability to communicate as a group in what has become known as quorum sensing (QS), and this trait has been associated with important bacterial phenotypes, such as virulence and biofilm formation. Bacteria also have an incredible ability to evolve resistance to all known antimicrobials. Hence, although inhibition of QS has been hailed as a means to reduce virulence in a manner that is impervious to bacterial resistance mechanisms, this approach is unlikely to be a panacea. Here we review the evidence that bacteria can evolve resistance to quorum-quenching compounds.201324014536
916510.9996Regulatory Mechanisms and Physiological Impacts of Quorum Sensing in Gram-Negative Bacteria. The Quorum sensing (QS) system is a widely existing communication mechanism, which regulates bacterial community behaviors and the expression of specific genes. The most common pathogenic bacteria in clinical infections are gram-negative bacteria, and QS plays an important regulatory role in the production of virulence factors and development of antibiotic resistance. This article reviews the QS systems of gram-negative bacteria and provides an overview of how they regulate their physiological functions.202439654694
916820.9996Novel approaches to bacterial infection therapy by interfering with bacteria-to-bacteria signaling. The growing challenge of antimicrobial resistance and the paucity of novel antibiotics underscore the importance of developing novel therapeutics. Bacterial cell-to-cell signaling constitutes a novel drug target. Quorum sensing (QS) is a cell-to-cell signaling mechanism that refers to the ability of bacteria to respond to chemical hormone-like molecules called autoinducers. QS is responsible for controlling a plethora of virulence genes in several bacterial pathogens. Antagonists to autoinducers will intercept bacterial intercellular communication, hindering their ability to act in a coordinated manner to express virulence traits. Moreover, since QS is not involved directly in essential processes, such as bacterial growth, one can reason that inhibition of QS will not yield a selective pressure for the development of resistance.200717402841
916030.9996Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective. Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria.201829563876
916440.9996Quorum quenching: role of nanoparticles as signal jammers in Gram-negative bacteria. Quorum sensingĀ (QS) is a cell density dependent regulatory process that uses signaling molecules to manage the expression of virulence genes and biofilm formation. The study of QS inhibitors has emerged as one of the most fascinating areas of research to discover novel antimicrobial agents. Compounds that block QS have become candidates as unusual antimicrobial agents, as they are leading players in the regulation of virulence of drug-resistant pathogens. Metal and metal oxide nanoparticles offer novel alternatives to combat antibiotic resistance in Gram-negative bacteria aiming their capacity as QS inhibitors. This review provides an insight into the quorum quenching potential of metal and metal oxide nanoparticles by targeting QS regulated virulence of Gram-negative bacteria.201930539663
913650.9996Histidine kinase-mediated signal transduction systems of pathogenic microorganisms as targets for therapeutic intervention. Pathogenic bacteria must be able to sense and respond rapidly to signals emanating from the host environment and use the signals to modulate the expression of genes required for the infection process. Two-component signal transduction systems, and their more complex variants known as phosphorelays, are woven within the fabric of bacterial cellular regulatory processes and are used to regulate the expression of genes involved in the virulence and antibiotic resistance responses of a large number of pathogens of major public health concern. The emergence of strains of pathogenic bacteria that are resistant to multiple antibiotics has driven the search for new targets and/or modes of action for anti-microbial agents. The presence of essential two-component systems in bacteria and the central role that these regulatory systems play in virulence and antibiotic resistance has meant that two-component systems and phosphorelays have been recognized as targets for antimicrobial intervention. This review will discuss the role of these signal transduction pathways in virulence responses and antibiotic sensitivity of pathogenic microorganisms and their potential use as targets for antimicrobial therapy. In addition, the current status on the development of inhibitors specific for two-component systems will be discussed.200212462127
916960.9996Interference of bacterial cell-to-cell communication: a new concept of antimicrobial chemotherapy breaks antibiotic resistance. Bacteria use a cell-to-cell communication activity termed "quorum sensing" to coordinate group behaviors in a cell density dependent manner. Quorum sensing influences the expression profile of diverse genes, including antibiotic tolerance and virulence determinants, via specific chemical compounds called "autoinducers". During quorum sensing, Gram-negative bacteria typically use an acylated homoserine lactone (AHL) called autoinducer 1. Since the first discovery of quorum sensing in a marine bacterium, it has been recognized that more than 100 species possess this mechanism of cell-to-cell communication. In addition to being of interest from a biological standpoint, quorum sensing is a potential target for antimicrobial chemotherapy. This unique concept of antimicrobial control relies on reducing the burden of virulence rather than killing the bacteria. It is believed that this approach will not only suppress the development of antibiotic resistance, but will also improve the treatment of refractory infections triggered by multi-drug resistant pathogens. In this paper, we review and track recent progress in studies on AHL inhibitors/modulators from a biological standpoint. It has been discovered that both natural and synthetic compounds can disrupt quorum sensing by a variety of means, such as jamming signal transduction, inhibition of signal production and break-down and trapping of signal compounds. We also focus on the regulatory elements that attenuate quorum sensing activities and discuss their unique properties. Understanding the biological roles of regulatory elements might be useful in developing inhibitor applications and understanding how quorum sensing is controlled.201323720655
913970.9996Contribution of quorum sensing to virulence and antibiotic resistance in zoonotic bacteria. Quorum sensing (QS), which is a key part of cell/cell communication, is widely distributed in microorganisms, especially in bacteria. Bacteria can produce and detect the presence of QS signal molecule, perceive the composition and density of microorganisms in their complex habitat, and then dynamically regulate their own gene expression to adapt to their environment. Among the many traits controlled by QS in pathogenic bacteria is the expression of virulence factors and antibiotic resistance. Many pathogenic bacteria rely on QS to govern the production of virulence factors and express drug-resistance, especially in zoonotic bacteria. The threat of antibiotic resistant zoonotic bacteria has called for alternative antimicrobial strategies that would mitigate the increase of classical resistance mechanism. Targeting QS has proven to be a promising alternative to conventional antibiotic for controlling infections. Here we review the QS systems in common zoonotic pathogenic bacteria and outline how QS may control the virulence and antibiotic resistance of zoonotic bacteria.202235487393
917180.9996Small molecules modulating AHL-based quorum sensing to attenuate bacteria virulence and biofilms as promising antimicrobial drugs. Clinically significant antibiotic resistance is one of the greatest challenges of the twenty-first century. Yet new antibiotics are currently being developed at a much slower pace than our growing need for such drugs. Instead of focusing on conventional therapeutics that target in vitro bacterial viability, an alternative therapy is to target virulence factors and biofilms. Such anti-virulence strategies have attracted more and more attention recently, for it would add both supplement and diversity to our current antimicrobial library. This approach has several potential advantages including imposing less evolutionary pressure on the development of antibiotic resistance, increasing the antibacterial targets and preserving the host endogenous microbiome. Quorum sensing is an intercellular communication process in bacterial communities, which can regulate coordinated expression of virulence factors and biofilms. N-Acyl homoserine lactones (AHLs) are autoinducers generated by a variety of Gram-negative bacteria. These signals combining with their cognate LuxR-type receptors trigger the expression of virulence genes. In this critical review, we summarize various structural types of small molecules targeting AHL-based quorum sensing to attenuate bacteria virulence factors and biofilms.201424164200
915990.9996Quorum sensing inhibitors (QSIs): a patent review (2019-2023). INTRODUCTION: The collective behavior of bacteria is regulated by Quorum Sensing (QS), in which bacteria release chemical signals and express virulence genes in a cell density-dependent manner. Quorum Sensing inhibitors (QSIs) are a large class of natural and synthetic compounds that have the potential to competitively inhibit the Quorum Sensing (QS) systems of several pathogens blocking their virulence mechanisms. They are considered promising compounds to deal with antimicrobial resistance, providing an opportunity to develop new drugs against these targets. AREAS COVERED: The present review represents a comprehensive analysis of patents and patent applications available on Espacenet and Google Patent, from 2019 to 2023 referring to the therapeutic use of Quorum Sensing inhibitors. EXPERT OPINION: Unlike classical antibiotics, which target the basic cellular metabolic processes, QSIs provide a promising alternative to attenuating virulence and pathogenicity without putting selective pressure on bacteria. The general belief is that QSIs pose no or little selective pressure on bacteria since these do not affect their growth. To date, QSIs are seen as the most promising alternative to traditional antibiotics. The next big step in this area of research is its succession to the clinical stage.202540219759
9166100.9996Mechanisms of Inhibition of Quorum Sensing as an Alternative for the Control of E. coli and Salmonella. Quorum sensing (QS) is a process of cell-cell communication for bacteria such as E. coli and Salmonella that cause foodborne diseases, with the production, release, and detection of autoinducer (AI) molecules that participate in the regulation of virulence genes. All of these proteins are useful in coordinating collective behavior, the expression of virulence factors, and the pathogenicity of Gram-negative bacteria. In this work, we review the natural or synthetic inhibitor molecules of QS that inactivate the autoinducer and block QS regulatory proteins in E. coli and Salmonella. Furthermore, we describe mechanisms of QS inhibitors (QSIs) that act as competitive inhibitors, being a useful tool for preventing virulence gene expression through the downregulation of AI-2 production pathways and the disruption of signal uptake. In addition, we showed that QSIs have negative regulatory activity of genes related to bacterial biofilm formation on clinical artifacts, which confirms the therapeutic potential of QSIs in the control of infectious pathogens. Finally, we discuss resistance to QSIs, the design of next-generation QSIs, and how these molecules can be leveraged to provide a new antivirulence therapy to combat diseases caused by E. coli or Salmonella.202235630329
9542110.9995Development of quorum-based anti-virulence therapeutics targeting Gram-negative bacterial pathogens. Quorum sensing is a cell density-dependent signaling phenomenon used by bacteria for coordination of population-wide phenotypes, such as expression of virulence genes, antibiotic resistance and biofilm formation. Lately, disruption of bacterial communication has emerged as an anti-virulence strategy with enormous therapeutic potential given the increasing incidences of drug resistance in pathogenic bacteria. The quorum quenching therapeutic approach promises a lower risk of resistance development, since interference with virulence generally does not affect the growth and fitness of the bacteria and, hence, does not exert an associated selection pressure for drug-resistant strains. With better understanding of bacterial communication networks and mechanisms, many quorum quenching methods have been developed against various clinically significant bacterial pathogens. In particular, Gram-negative bacteria are an important group of pathogens, because, collectively, they are responsible for the majority of hospital-acquired infections. Here, we discuss the current understanding of existing quorum sensing mechanisms and present important inhibitory strategies that have been developed against this group of pathogenic bacteria.201323939429
9133120.9995Overcoming antimicrobial resistance by targeting resistance mechanisms. Three mechanisms of antimicrobial resistance predominate in bacteria: antibiotic inactivation, target site modification, and altered uptake by way of restricted entry and/or enhanced efflux. Many of these involve enzymes or transport proteins whose activity can be targeted directly in an attemptto compromise resistance and, thus, potentiate antimicrobial activity. Alternatively, novel agents unaffected by these resistance mechanisms can be developed. Given the ongoing challenge posed by antimicrobial resistance in bacteria, targeting resistance in this way may be our best hope at prolonging the antibiotic era.200111291743
9113130.9995Quorum Sensing Inhibition or Quenching in Acinetobacter baumannii: The Novel Therapeutic Strategies for New Drug Development. Acinetobacter baumannii is a Gram-negative opportunistic nosocomial pathogen, which can cause ventilator-related and blood infection in critically ill patients. The resistance of A. baumannii clinical isolates to common antimicrobials and their tolerance to desiccation have emerged as a serious problem to public health. In the process of pathogenesis, bacteria release signals, which regulate virulence and pathogenicity-related genes. Such bacteria coordinate their virulent behavior in a cell density-dependent phenomenon called quorum sensing (QS). In contrast, the two main approaches of QS interference, quorum sensing inhibitors (QSIs) and quorum quenching (QQ) enzymes, have been developed to reduce the virulence of bacteria, thus reducing the pressure to produce bacterial drug resistance. Therefore, QSIs or QQ enzymes, which interfere with these processes, might potentially inhibit bacterial QS and ultimately biofilm formation. In this review, we aim to describe the state-of-art in the QS process in A. baumannii and elaborate on the use of QSIs or QQ enzymes as antimicrobial drugs in various potential sites of the QS pathway.202133597937
8290140.9995Antimicrobial Peptides: Features, Action, and Their Resistance Mechanisms in Bacteria. In recent years, because of increased resistance to conventional antimicrobials, many researchers have started to study the synthesis of new antibiotics to control the disease-causing effects of infectious pathogens. Antimicrobial peptides (AMPs) are among the newest antibiotics; these peptides are integral compounds in all kinds of organisms and play a significant role in microbial ecology, and critically contribute to the innate immunity of organisms by destroying invading microorganisms. Moreover, AMPs may encourage cells to produce chemokines, stimulate angiogenesis, accelerate wound healing, and influence programmed cell death in multicellular organisms. Bacteria differ in their inherent susceptibility and resistance mechanisms to these peptides when responding to the antimicrobial effects of AMPs. Generally, the development of AMP resistance mechanisms is driven by direct competition between bacterial species, and host and pathogen interactions. Several studies have shown diverse mechanisms of bacterial resistance to AMPs, for example, some bacteria produce proteases and trapping proteins; some modify cell surface charge, change membrane fluidity, and activate efflux pumps; and some species make use of biofilms and exopolymers, and develop sensing systems by selective gene expression. A closer understanding of bacterial resistance mechanisms may help in developing novel therapeutic approaches for the treatment of infections caused by pathogenic organisms that are successful in developing extensive resistance to AMPs. Based on these observations, this review discusses the properties of AMPs, their targeting mechanisms, and bacterial resistance mechanisms against AMPs.201829957118
9158150.9995Quorum sensing pathways in Gram-positive and -negative bacteria: potential of their interruption in abating drug resistance. Quorum sensing (QS) is an inter-cell communication between bacterial populations through release of tiny diffusible compounds as signalling agents, called auto-inducers, abetting bacteria to track population density. QS allows bacterial population to perform collectively in coordination to wide phenotypes like alterations in expression of virulence genes to achieve advancement over their competitors, drug resistance and biofilm formation. Several classes of autoinducers have been described that are involved in bacterial virulence. This review gives an insight into the multitudinous QS systems in Gram-positive and Gram-negative bacteria to explore their role in microbial physiology and pathogenesis. Bacterial resistance to antibiotics has clinically become a super challenge. Strategies to interrupt QS pathways by natural and synthetic QS inhibitors or quorum quenchers or analogs provide a potential treatment. We highlight the advancements in discovery of promising new targets for development of next generation antimicrobials to control infections caused by multidrug resistant bacterial pathogens.201931007147
8242160.9995New antibacterial targets: Regulation of quorum sensing and secretory systems in zoonotic bacteria. Quorum sensing (QS) is a communication mechanism that controls bacterial communication and can influence the transcriptional expression of multiple genes through one or more signaling molecules, thereby coordinating the population response of multiple bacterial pathogens. Secretion systems (SS) play an equally important role in bacterial information exchange, relying on the secretory systems to secrete proteins that act as virulence factors to promote adhesion to host cells. Eight highly efficient SS have been described, all of which are involved in the secretion or transfer of virulence factors, and the effector proteins they secrete play a key role in the virulence and pathogenicity of bacteria. It has been shown that many bacterial SS are directly or indirectly regulated by QS and thus influence bacterial virulence and antibiotic resistance. This review describes the relationship between QS and SS of several common zoonotic pathogenic bacteria and outlines the molecular mechanisms of how QS systems regulate SS, to provide a theoretical basis for the study of bacterial pathogenicity and the development of novel antibacterial drugs.202337343493
8289170.9995Roles of Regulatory RNAs for Antibiotic Resistance in Bacteria and Their Potential Value as Novel Drug Targets. The emergence of antibiotic resistance mechanisms among bacterial pathogens increases the demand for novel treatment strategies. Lately, the contribution of non-coding RNAs to antibiotic resistance and their potential value as drug targets became evident. RNA attenuator elements in mRNA leader regions couple expression of resistance genes to the presence of the cognate antibiotic. Trans-encoded small RNAs (sRNAs) modulate antibiotic tolerance by base-pairing with mRNAs encoding functions important for resistance such as metabolic enzymes, drug efflux pumps, or transport proteins. Bacteria respond with extensive changes of their sRNA repertoire to antibiotics. Each antibiotic generates a unique sRNA profile possibly causing downstream effects that may help to overcome the antibiotic challenge. In consequence, regulatory RNAs including sRNAs and their protein interaction partners such as Hfq may prove useful as targets for antimicrobial chemotherapy. Indeed, several compounds have been developed that kill bacteria by mimicking ligands for riboswitches controlling essential genes, demonstrating that regulatory RNA elements are druggable targets. Drugs acting on sRNAs are considered for combined therapies to treat infections. In this review, we address how regulatory RNAs respond to and establish resistance to antibiotics in bacteria. Approaches to target RNAs involved in intrinsic antibiotic resistance or virulence for chemotherapy will be discussed.201728529506
9125180.9995Coevolution of Resistance Against Antimicrobial Peptides. Antimicrobial peptides (AMPs) are produced by all forms of life, ranging from eukaryotes to prokaryotes, and they are a crucial component of innate immunity, involved in clearing infection by inhibiting pathogen colonization. In the recent past, AMPs received high attention due to the increase of extensive antibiotic resistance by these pathogens. AMPs exhibit a diverse spectrum of activity against bacteria, fungi, parasites, and various types of cancer. AMPs are active against various bacterial pathogens that cause disease in animals and plants. However, because of the coevolution of host and pathogen interaction, bacteria have developed the mechanisms to sense and exhibit an adaptive response against AMPs. These resistance mechanisms are playing an important role in bacterial virulence within the host. Here, we have discussed the different resistance mechanisms used by gram-positive and gram-negative bacteria to sense and combat AMP actions. Understanding the mechanism of AMP resistance may provide directions toward the development of novel therapeutic strategies to control multidrug-resistant pathogens.202032119634
9134190.9995Mechanism of drug resistance in bacteria: efflux pump modulation for designing of new antibiotic enhancers. Drug resistance has now become a serious concern in the domain of microbial infection. Bacteria are becoming smarter by displaying a variety of mechanisms during drug resistance. It is not only helping bacteria to adapt nicely in adverse environment but it also makes a smart system for better availability of nutritional status for microorganisms. In this domain, pathogenic bacteria are extensively studied and their mechanism for drug resistance is well explored. The common modes in bacterial resistance include degradation of antibiotics by enzymes, antibiotic target modification or inactivation by enzymatic actions, complete replacement of antibiotic targets, quorum sensing (QS) mechanism, and efflux pump-based extrusion of antibiotics. In this review, various mechanisms of drug resistance in bacteria have been highlighted with giving the importance of efflux pumps. This can be explored as a knowledge source for the management of a variety of bacterial infections, related disease and vibrant clue for next-generation drug development.202134431062