Mechanisms of Inhibition of Quorum Sensing as an Alternative for the Control of E. coli and Salmonella. - Related Documents




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916601.0000Mechanisms 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
916510.9999Regulatory 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
911320.9999Quorum 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
916430.9998Quorum quenching: role of nanoparticles as signal jammers in Gram-negative bacteria. Quorum sensing (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
916740.9998Bioactive proteins from Solanaceae as quorum sensing inhibitors against virulence in Pseudomonas aeruginosa. Cell-to-cell communication or quorum sensing (QS) is a generic event in bacteria that is used to coordinate gene expression among local populations. The phenomenon of QS depends on the fact that presence of sufficient bacteria ascertains a threshold level of autoinducer concentration that allows bacteria to sense a critical cell mass and to activate or repress target genes. Thus, QS has been an attractive target for the development of anti-infective strategies that are not based on the use of antibiotics. Several anti-QS approaches have been demonstrated including natural products from plant-based secondary metabolites. However, the role of plant bioactive proteins as an anti-QS peptide is yet to be deciphered. Against a backdrop of ever-increasing antibiotic resistant pathogens, there is a strong need for development of alternative therapeutic strategies. Thus, our hypothesis is that bioactive proteins from the plant family Solanaceae are quorum quenching molecules that can be exploited to develop a therapeutic strategy against virulence. We presume that bioactive proteins will inactivate or inhibit or degrade QS signals from bacteria to prevent cell-to-cell communication and thus inhibit development of virulence in Pseudomonas aeruginosa. Further, the use of proteins as quorum quenchers will delay the bacteria to develop resistance against these quenching molecules.201525777471
916850.9998Novel 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
917060.9998It is the time for quorum sensing inhibition as alternative strategy of antimicrobial therapy. Multiple drug resistance poses a significant threat to public health worldwide, with a substantial increase in morbidity and mortality rates. Consequently, searching for novel strategies to control microbial pathogenicity is necessary. With the aid of auto-inducers (AIs), quorum sensing (QS) regulates bacterial virulence factors through cell-to-cell signaling networks. AIs are small signaling molecules produced during the stationary phase. When bacterial cultures reach a certain level of growth, these molecules regulate the expression of the bound genes by acting as mirrors that reflect the inoculum density.Gram-positive bacteria use the peptide derivatives of these signaling molecules, whereas Gram-negative bacteria use the fatty acid derivatives, and the majority of bacteria can use both types to modulate the expression of the target gene. Numerous natural and synthetic QS inhibitors (QSIs) have been developed to reduce microbial pathogenesis. Applications of QSI are vital to human health, as well as fisheries and aquaculture, agriculture, and water treatment. Video Abstract.202337316831
888470.9998Regulatory Mechanisms of the LuxS/AI-2 System and Bacterial Resistance. The quorum-sensing (QS) system is an intercellular cell-cell communication mechanism that controls the expression of genes involved in a variety of cellular processes and that plays critical roles in the adaption and survival of bacteria in their environment. The LuxS/AI-2 QS system, which uses AI-2 (autoinducer-2) as a signal molecule, has been identified in both Gram-negative and Gram-positive bacteria. As one of the important global regulatory networks in bacteria, it responds to fluctuations in the numbers of bacteria and regulates the expression of a number of genes, thus affecting cell behavior. We summarize here the known relationships between the LuxS/AI-2 system and drug resistance, discuss the inhibition of LuxS/AI-2 system as an approach to prevent bacterial resistance, and present new strategies for the treatment of drug-resistant pathogens.201931383657
954280.9998Development 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
916990.9998Interference 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
8885100.9998The LuxS/AI-2 system of Streptococcus suis. Quorum sensing (QS) is an important protective mechanism that allows bacteria to adapt to its environment. A limited number of signal molecules play the key role of transmitting information in this mechanism. Signals are transmitted between individual bacterium through QS systems, resulting in the expression of specific genes. QS plays an important role in a variety of bacterial processes, including drug resistance, biofilm formation, motility, adherence, and virulence. Most Gram-positive and Gram-negative bacteria possess QS systems, mainly the LuxS/AI-2-mediated QS system. Evidence has been brought that LuxS/AI-2 system controls major virulence determinants in Streptococcus suis and, as such, the ability of this bacterial species to cause infections in humans and pigs. Understanding the S. suis LuxS/AI-2 system may open up novel avenues for decreasing the drug resistance and infectivity of S. suis. This article focuses on the progress made to date on the S. suis LuxS/AI-2-mediated QS system.201829938319
9159110.9998Quorum 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
9163120.9998Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with growth. Compounds that can override communication signals have been found in the marine environment. Using Pseudomonas aeruginosa PAO1 as an example of an opportunistic human pathogen, we show that a synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing systems and inhibited virulence factor expression. Application of the drug to P.aeruginosa biofilms increased bacterial susceptibility to tobramycin and SDS. In a mouse pulmonary infection model, the drug inhibited quorum sensing of the infecting bacteria and promoted their clearance by the mouse immune response.200312881415
9171130.9997Small 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
8242140.9997New 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
9139150.9997Contribution 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
9125160.9997Coevolution 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
9158170.9997Quorum 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
9137180.9997Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy. Two-component signal transduction systems are central elements of the virulence and antibiotic resistance responses of opportunistic bacterial pathogens. These systems allow the bacterium to sense and respond to signals emanating from the host environment and to modulate the repertoire of genes expressed to allow invasion and growth in the host. The integral role of two-component systems in virulence and antibiotic sensitivity, and the existence of essential two-component systems in several pathogenic bacteria, suggests that these systems may be novel targets for antimicrobial intervention. This review discusses the potential use of two-component systems as targets for antimicrobial therapy against Gram-positive pathogens and the current status in the development of inhibitors specific for these systems.200212191621
9136190.9997Histidine 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