Search Results (33)

Antibiotic resistance is a major problem and a major global health concern. In total, there are 16 million deaths yearly from infectious diseases, and at least 65% of infectious diseases are caused by microbial communities that proliferate through the formation of biofilms. Antibiotic overuse has resulted in the evolution of multidrug-resistant (MDR) microbial strains. As a result, there is now much more interest in non-antibiotic therapies for bacterial infections. Among these revolutionary, non-traditional medications is quorum sensing inhibitors (QSIs). Bacterial cell-to-cell communication is known as quorum sensing (QS), and it is mediated by tiny diffusible signaling molecules known as autoinducers (AIs). QS is dependent on the density of the bacterial population. QS is used by Gram-negative and Gram-positive bacteria to control a wide range of processes; in both scenarios, QS entails the synthesis, identification, and reaction to signaling chemicals, also known as auto-inducers. Since the usual processes regulated by QS are the expression of virulence factors and the creation of biofilms, QS is being investigated as an alternative solution to antibiotic resistance. Consequently, the use of QS-inhibiting agents, such as QSIs and quorum quenching (QQ) enzymes, to interfere with QS seems like a good strategy to prevent bacterial infections. This review sheds light on QS inhibition strategy and mechanisms and discusses how using this approach can aid in winning the battle against resistant bacteria. Full article

With the widespread phenomenon of antibiotic resistance and the diffusion of multiple drug-resistant bacterial strains, enormous efforts are being conducted to identify suitable alternative agents against pathogenic microorganisms. Since an association between biofilm formation and antibiotic resistance phenotype has been observed, a promising strategy pursued in recent years focuses on controlling and preventing this formation by targeting and inhibiting the Quorum Sensing (QS) system, whose central role in biofilm has been extensively demonstrated. Therefore, the research and development of Quorum Quenching (QQ) compounds, which inhibit QS, has gradually attracted the attention of researchers and has become a new strategy for controlling harmful microorganisms. Among these, a number of both natural and synthetic compounds have been progressively identified as able to interrupt the intercellular communication within a microbial community and the adhesion to a surface, thus disintegrating mature/preformed biofilms. This review describes the role played by QS in the formation of bacterial biofilms and then focuses on the mechanisms of different natural and synthetic QS inhibitors (QSIs) exhibiting promising antibiofilm ability against Gram-positive and Gram-negative bacterial pathogens and on their applications as biocontrol strategies in various fields. Full article

In the new antibiotic era, the exponential increase in multiresistant bacterial strains has become the main global health problem. Many researchers have focused their efforts on exploring novel or combined strategies for combating bacterial resistance. Good knowledge of the molecular mechanisms of resistance and bacterial virulence factors as key targets provides us with a good basis for resolving the problem. One particularly attractive and promising strategy is to attack the main regulatory “network” of bacterial virulence determinants known as quorum sensing (QS). The inhibition of QS signals will be a novel means of screening more effective quorum-sensing inhibitors (QSIs) and will play a key role in the use of next-generation antimicrobials in the battle against resistance. This motivated the present review to provide a comprehensive clarification of the regulatory mechanisms of quorum-sensing signaling pathways in Chromobacterium violaceum and the discovery of potential plant quorum-sensing inhibitors. Full article

Pseudomonas aeruginosa is an opportunistic pathogen that infects patients by regulating virulence factors and biofilms through a quorum sensing (QS) system to protect itself from antibiotics and environmental stress. Therefore, the development of quorum sensing inhibitors (QSIs) is expected to become a new strategy for studying drug resistance to P. aeruginosa infections. Marine fungi are valuable resources for screening QSIs. A marine fungus, Penicillium sp. JH1, with anti-QS activity was isolated from the offshore waters of Qingdao (China), and citrinin, a novel QSI, was purified from secondary metabolites of this fungus. Citrinin could significantly inhibit the production of violacein in Chromobacterium violaceum CV12472 and the production of three virulence factors (elastase, rhamnolipid and pyocyanin) in P. aeruginosa PAO1. It could also inhibit the biofilm formation and motility of PAO1. In addition, citrinin downregulated the transcript levels of nine genes (lasI, rhlI, pqsA, lasR, rhlR, pqsR, lasB, rhlA and phzH) associated with QS. Molecular docking results showed that citrinin bound to PqsR and LasR with better affinity than the natural ligands. This study laid a foundation for the further study of the structure optimization and structure–activity relationship of citrinin. Full article

Quorum sensing (QS) is a cell-to-cell communication mechanism that regulates bacterial pathogenicity, biofilm formation, and antibiotic sensitivity. Among the identified quorum sensing, AI-2 QS exists in both Gram-negative and Gram-positive bacteria and is responsible for interspecies communication. Recent studies have highlighted the connection between the phosphotransferase system (PTS) and AI-2 QS, with this link being associated with protein-protein interaction (PPI) between HPr and LsrK. Here, we first discovered several AI-2 QSIs targeting the LsrK/HPr PPI site through molecular dynamics (MD) simulation, virtual screening, and bioassay evaluation. Of the 62 compounds purchased, eight compounds demonstrated significant inhibition in LsrK-based assays and AI-2 QS interference assays. Surface plasmon resonance (SPR) analysis confirmed that the hit compound 4171-0375 specifically bound to the LsrK-N protein (HPr binding domain, KD = 2.51 × 10⁻⁵ M), and therefore the LsrK/HPr PPI site. The structure-activity relationships (SARs) emphasized the importance of hydrophobic interactions with the hydrophobic pocket and hydrogen bonds or salt bridges with key residues of LsrK for LsrK/HPr PPI inhibitors. These new AI-2 QSIs, especially 4171-0375, exhibited novel structures, significant LsrK inhibition, and were suitable for structural modification to search for more effective AI-2 QSIs. Full article

Experience-based knowledge has shown that bacteria can communicate with each other through a cell-density-dependent mechanism called quorum sensing (QS). QS controls specific bacterial phenotypes, such as sporulation, virulence and pathogenesis, the production of degrading enzymes, bioluminescence, swarming motility, and biofilm formation. The expression of these phenotypes in food spoiling and pathogenic bacteria, which may occur in food, can have dramatic consequences on food production, the economy, and health. Due to the many reports showing that the use of conventional methods (i.e., antibiotics and sanitizers) to inhibit bacterial growth leads to the emergence of antibiotic resistance, it is necessary to research and exploit new strategies. Several studies have already demonstrated positive results in this direction by inhibiting autoinducers (low-molecular-weight signaling compounds controlling QS) and by other means, leading to QS inhibition via a mechanism called quorum quenching (QQ). Thus far, several QS inhibitors (QSIs) have been isolated from various sources, such as plants, some animals from aqueous ecosystems, fungi, and bacteria. The present study aims to discuss the involvement of QS in food spoilage and to review the potential role of probiotics as QSIs. Full article

Streptococcus suis (S. suis) is an important zoonotic pathogen. It mainly uses quorum sensing (QS) to adapt to complex and changeable environments. QS is a universal cell-to-cell communication system that has been widely studied for its physiological functions, including the regulation of bacterial adhesion, virulence, and biofilm formation. Quorum sensing inhibitors (QSIs) are highly effective at interfering with the QS system and bacteria have trouble developing resistance to them. We review the current research status of the S. suis LuxS/AI-2 QS system and QSIs. Studies showed that by inhibiting the formation of AI-2, targeting the LuxS protein, inhibiting the expression of luxs gene can control the LuxS/AI-2 QS system of S. suis. Other potential QSIs targets are summarized, which may be preventing and treating S. suis infections, including AI-2 production, transmission, LuxS protein, blockage of AI-2 binding to receptors, AI-2-mediated QS. Since antibiotics are becoming increasingly ineffective due to the emergence of resistant bacteria, including S. suis, it is thus critical to find new antibacterial drugs with different mechanisms of action. QSIs provide hope for the development of such drugs. Full article

Microbial spoilage of fish is attributed to quorum sensing (QS)-based activities. QS is a communication process between the cells in which microorganisms secrete and sense the specific chemicals (autoinductors, AIs) that regulate proteolysis, lipolysis, and biofilm formation. These activities change the organoleptic characteristics and reduce the safety of the products. Although the microbial community of fish is diverse and may consist of a range of bacterial strains, the deterioration of fish-based products is attributed to the growth and activity of Pseudomonas spp. This work summarizes recent advancements to assess the influence of QS mechanisms on seafood spoilage by Pseudomonas spp. The quorum sensing inhibition (QSI) in the context of fish preservation has also been discussed. Detailed recognition of this phenomenon is crucial in establishing effective strategies to prevent the premature deterioration of fish-based products. Full article

Quorum sensing (QS) regulates the expression of several genes including motility, biofilm development, virulence expression, population density detection and plasmid conjugation. It is based on “autoinducers”, small molecules that microorganisms produce and release in the extracellular milieu. The biochemistry of quorum sensing is widely discussed and numerous papers are available to scientists. The main purpose of this research is to understand how knowledge about this mechanism can be exploited for the benefit of humans and the environment. Here, we report the most promising studies on QS and their resulting applications in different fields of global interest: food, agriculture and nanomedicine. Full article

Natural products derived from marine sponges have exhibited bioactivity and, in some cases, serve as potent quorum sensing inhibitory agents that prevent biofilm formation and attenuate virulence factor expression by pathogenic microorganisms. In this study, the inhibitory activity of the psammaplin-type compounds, psammaplin A (1) and bisaprasin (2), isolated from the marine sponge, Aplysinellarhax, are evaluated in quorum sensing inhibitory assays based on the Pseudomonas aeruginosa PAO1 lasB-gfp(ASV) and rhlA-gfp(ASV) biosensor strains. The results indicate that psammaplin A (1) showed moderate inhibition on lasB-gfp expression, but significantly inhibited the QS-gene promoter, rhlA-gfp, with IC₅₀ values at 14.02 μM and 4.99 μM, respectively. In contrast, bisaprasin (2) displayed significant florescence inhibition in both biosensors, PAO1 lasB-gfp and rhlA-gfp, with IC₅₀ values at 3.53 μM and 2.41 μM, respectively. Preliminary analysis suggested the importance of the bromotyrosine and oxime functionalities for QSI activity in these molecules. In addition, psammaplin A and bisaprasin downregulated elastase expression as determined by the standard enzymatic elastase assay, although greater reduction in elastase production was observed with 1 at 50 μM and 100 μM. Furthermore, the study revealed that bisaprasin (2) reduced biofilm formation in P. aeruginosa. Full article

Increased resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. (ESKAPE) pathogens against various drugs has enhanced the urge for the development of alternate therapeutics. Quorum sensing (QS) is a density dependent cell-to-cell communication mechanism responsible for controlling pathogenicity with the regulation of gene expression. Thus, QS is considered a potential target for the development of newer anti-biofilm agents that do not depend on the utilization of antibiotics. Compounds with anti-QS effects are known as QS inhibitors (QSIs), and they can inhibit the QS mechanism that forms the major form in the development of bacterial pathogenesis. A diverse array of natural compounds provides a plethora of anti-QS effects. Over recent years, these natural compounds have gained importance as new strategies for combating the ESKAPE pathogens and inhibiting the genes involved in QS. Different pharmacognostical and pharmacological studies have been carried out so far for identification of novel drugs or for the discovery of their unique structures that may help in developing more effective anti-biofilm therapies. The main objective of this review is to discuss the various natural compounds, so far identified and their employed mechanisms in hindering the genes responsible for QS leading to bacterial pathogenesis. Full article

The biological control of plant pathogens is linked to the composition and activity of the plant microbiome. Plant-associated microbiomes co-evolved with land plants, leading to plant holobionts with plant-beneficial microbes but also with plant pathogens. A diverse range of plant-beneficial microbes assists plants to reach their optimal development and growth under both abiotic and biotic stress conditions. Communication within the plant holobiont plays an important role, and besides plant hormonal interactions, quorum-sensing signalling of plant-associated microbes plays a central role. Quorum-sensing (QS) autoinducers, such as N-acyl-homoserine lactones (AHL) of Gram-negative bacteria, cause a pronounced interkingdom signalling effect on plants, provoking priming processes of pathogen defence and insect pest control. However, plant pathogenic bacteria also use QS signalling to optimise their virulence; these QS activities can be controlled by quorum quenching (QQ) and quorum-sensing inhibition (QSI) approaches by accompanying microbes and also by plants. Plant growth-promoting bacteria (PGPB) have also been shown to demonstrate QQ activity. In addition, some PGPB only harbour genes for AHL receptors, so-called luxR-solo genes, which can contribute to plant growth promotion and biological control. The presence of autoinducer solo receptors may reflect ongoing microevolution processes in microbe–plant interactions. Different aspects of QS systems in bacteria–plant interactions of plant-beneficial and pathogenic bacteria will be discussed, and practical applications of bacteria with AHL-producing or -quenching activity; QS signal molecules stimulating pathogen control and plant growth promotion will also be presented. Full article

The development of microbial resistance requires a novel approach to control microbial infection. This study implies the microbial synthesis of nanometals and assessment of their antivirulent activity against Pseudomonas aeruginosa. Streptomyces isolate S91 was isolated from soil with substantial ability for growth at high salts concentrations. The cell-free supernatant of S91was utilized for the synthesis of Au-NPs and Se-NPs. The 16S rRNA sequence analysis of Streptomyces S91 revealed that S91 had a high similarity (98.82%) to Streptomyces olivaceous. The biosynthesized Au-NPs and Se-NPs were characterized using a UV-Vis spectrophotometer, dynamic light scattering, transmission electron microscopy, energy dispersive X-ray diffraction and Fourier-transform infrared spectroscopy. The quorum sensing inhibitory (QSI) potential of Au-NPs and Se-NPs and the antivirulence activity was examined against P. aeruginosa. The QSI potential was confirmed using RT-PCR. The synthesized Au-NPs and Se-NPs were monodispersed spherical shapes with particle size of 12.2 and 67.98 nm, respectively. Au-NPs and Se-NPs eliminated QS in P. aeruginosa at a concentration range of 2.3–18.5 µg/mL for Au-NPs and 2.3–592 µg/mL for Se-NPs. In addition, Au-NPs and Se-NPs significantly inhibited QS-related virulence factors, such as pyocyanin, protease and, elastase in P. aeruginosa. At the molecular level, Au-NPs and Se-NPs significantly suppressed the relative expression of QS genes and toxins. Hence, the biosynthesized Au-NPS and Se-NPS could be substantial inhibitors of QS and virulence traits of P. aeruginosa. Full article

Pseudomonas aeruginosa, an important opportunistic pathogen, is capable of producing various virulence factors and forming biofilm that are regulated by quorum sensing (QS). It is known that targeting virulence factor production and biofilm formation instead of exerting selective pressure on growth such as conventional antibiotics can reduce multidrug resistance in bacteria. Therefore, many quorum-sensing inhibitors (QSIs) have been developed to prevent or treat this bacterial infection. In this study, wogonin, as an active ingredient from Agrimonia pilosa, was found to be able to inhibit QS system of P. aeruginosa PAO1. Wogonin downregulated the expression of QS-related genes and reduced the production of many virulence factors, such as elastase, pyocyanin, and proteolytic enzyme. In addition, wogonin decreased the extracellular polysaccharide synthesis and inhibited twitching, swimming, and swarming motilities and biofilm formation. The attenuation of pathogenicity in P. aeruginosa PAO1 by wogonin application was further validated in vivo by cabbage infection and fruit fly and nematode survival experiments. Further molecular docking analysis, pathogenicity examination of various QS-related mutants, and PQS signal molecule detection revealed that wogonin could interfere with PQS signal molecular synthesis by affecting pqsA and pqsR. Taken together, the results indicated that wogonin might be used as an anti-QS candidate drug to attenuate the infection caused by P. aeruginosa. Full article

Quorum sensing (QS) is employed by the opportunistic pathogen Pseudomonas aeruginosa to regulate physiological behaviors and virulence. QS inhibitors (QSIs) are potential anti-virulence agents for the therapy of P. aeruginosa infection. During the screening for QSIs from Chinese herbal medicines, falcarindiol (the major constituent of Notopterygium incisum) exhibited QS inhibitory activity. The subinhibitory concentration of falcarindiol exerted significant inhibitory effects on the formation of biofilm and the production of virulence factors such as elastase, pyocyanin, and rhamnolipid. The mRNA expression of QS-related genes (lasB, phzH, rhlA, lasI, rhlI, pqsA, and rhlR) was downregulated by falcarindiol while that of lasR was not affected by falcarindiol. The transcriptional activation of the lasI promoter was inhibited by falcarindiol in the P. aeruginosa QSIS-lasI selector. Further experiments confirmed that falcarindiol inhibited the las system using the reporter strain Escherichia coli MG4/pKDT17. Electrophoretic mobility shift assay (EMSA) showed that falcarindiol inhibited the binding of the transcription factor LasR and the lasI promoter region. Molecular docking showed that falcarindiol interacted with the Tyr47 residue, leading to LasR instability. The decrease of LasR-mediated transcriptional activation was responsible for the reduction of downstream gene expression, which further inhibited virulence production. The inhibition mechanism of falcarindiol to LasR provides a theoretical basis for its medicinal application. Full article