Search Results (532)

Ginkgetin (GK) is a naturally occurring biflavonoid predominantly isolated from Ginkgo biloba and has attracted increasing attention because of its broad pharmacological activities. Structurally, GK belongs to the 3′-8″-linked biflavone subclass, which distinguishes it from other biflavonoids like amentoflavone (the parent compound of this subclass) and its monomeric counterparts such as apigenin. This unique C-C linked dimeric architecture confers distinct molecular planarity and lipophilicity, contributing to its enhanced membrane permeability and multitarget engagement capabilities. GK has been shown to exert pleiotropic biological effects in preclinical studies, including anti-inflammatory, antioxidant, antifibrotic, anticancer, neuroprotective, cardioprotective, metabolic regulatory and antibacterial activities. Mechanistically, preclinical evidence indicates that GK functions as a multitarget modulator of key signaling pathways involved in oxidative stress, inflammation, cell death and tissue remodeling, such as nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1), nuclear factor kappa-B(NF-κB), Janus kinase/signal transducer and activator of transcription(JAK/STAT), mitogen-activated protein kinases(MAPKs), AMP-activated protein kinase/mechanistic target of rapamycin(AMPK/mTOR), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) and cyclic GMP-AMP synthase–stimulator of interferon genes(cGAS–STING). Notably, GK has been observed to display context-dependent regulation of cell fate decisions, including apoptosis, autophagy and ferroptosis, thereby enabling the selective elimination of pathological cells while preserving normal tissue function. Preclinical studies further demonstrate that GK exhibits therapeutic potential across diverse disease systems, including cancer, metabolic disorders, cardiovascular diseases, neurological disorders and musculoskeletal diseases. In addition, emerging evidence highlights its antibacterial and antivirulence properties through the inhibition of biofilm formation and quorum sensing. It is crucial to note, however, that this promising profile is predominantly derived from preclinical studies, and clinical evidence in humans remains to be established. Despite these promising findings, the clinical translation of GK remains limited by challenges related to pharmacokinetics, bioavailability and druggability. This review systematically summarizes the chemical characteristics, pharmacological activities and molecular mechanisms of GK, with an emphasis on its multitarget actions and therapeutic potential across disease systems, and discusses current limitations and future perspectives to facilitate the rational development of GK-based interventions. Full article

Lactiplantibacillus plantarum EL2, isolated from traditional fermented yak milk in the high-altitude Gannan Tibetan Autonomous Prefecture, produces the class IIb bacteriocin PlnJK. This study established three distinct cultivation models that critically influenced bacteriocin yield. Microbial co-culture was found to enhance the stress tolerance of EL2, significantly boosting PlnJK production. The optimal inducing strain, Enterococcus faecalis MH2, increased the bacteriocin inhibition zone diameter from 15.38 mm to 25.58 mm. Following optimization of key parameters—initial inoculum concentration (10⁷ CFU/mL), inoculation ratio (3:1, EL2:MH2), and initial pH (6.0)—the inhibition zone diameter reached 30.32 mm, representing a 1.97-fold increase over pure culture. Co-culture not only advanced the onset but also extended the duration of bacteriocin synthesis. Throughout the 24 h incubation, cell density, AI-2 autoinducer concentration, and the expression of key regulatory genes were significantly elevated in co-culture compared to monoculture, aligning with a cell-density-dependent, quorum-sensing (QS) regulatory paradigm. Bacteriocin production was co-regulated by two QS pathways: the AI-2/luxS system and the plnA-mediated autoinducing peptide (AIP). Gene expression analysis revealed differential temporal regulation: luxS expression was higher during the exponential phase (2.29 vs. 1.42 in stationary phase), while plnA exhibited the opposite pattern (1.42 in exponential vs. 2.21 in stationary phase). This indicates that the AI-2/luxS pathway drives strong induction during active growth, whereas plnA/AIP-mediated promotion becomes predominant later. The stationary-phase effect is likely triggered by the accumulation of specific MH2 metabolites, which impose an environmental stress on EL2, stimulating the pln-encoded regulatory system and further enhancing bacteriocin yield. This work provides an economically viable strategy and a novel theoretical framework for optimizing microbial cultivation, enhancing bacteriocin production, and elucidating the complex QS-mediated regulatory mechanisms involved. Full article

Antimicrobial resistance (AMR) is one of the most pressing global public health challenges, compromising the effectiveness of standard antibiotic therapies and increasing morbidity, mortality, and healthcare costs. The scarcity of new antibiotics has driven research into alternative strategies to restore or enhance the effectiveness of existing drugs. Natural compounds, including polyphenols, alkaloids, terpenes and terpenoids, antimicrobial peptides, and microbial secondary metabolites, exhibit multitarget activities such as membrane disruption, efflux pump inhibition, biofilm suppression, and quorum sensing interference. In parallel, synthetic and semi-synthetic small-molecule inhibitors have been rationally designed to target specific resistance determinants, including β-lactamases, efflux systems, quorum sensing pathways, and stress-induced mutagenesis mechanisms such as the SOS response and DNA repair processes. These agents act as adjuvants, restoring susceptibility or reducing bacterial virulence without exerting strong selective pressure. The integration of natural bioactive compounds and targeted small-molecule inhibitors represents a promising complementary strategy for conventional antibiotics. Further pharmacological and clinical investigations are required to translate these approaches into effective tools within antimicrobial stewardship programs and broader public health strategies aimed at mitigating the global burden of AMR. This narrative review analyses the recent literature on natural compounds and synthetic or semi-synthetic small-molecule inhibitors with documented activity against antimicrobial resistance mechanisms. Full article

Vibrio alginolyticus is a foodborne pathogen commonly found in seafood and freshwater products, causing human illness through the consumption of tainted seafood. Small non-coding RNAs (sRNAs) take effect on the stability and translation of their target mRNAs by base-pairing, thereby quickly altering bacterial physiology and pathogenicity at the post-transcriptional level. This work constructed a label-free in-frame deletion mutant and a complement strain of micX, a cell-density-associated sRNA in V. alginolyticus. The ΔmicX mutant exhibited reduced growth and a reduction in the synthesis of exopolysaccharides, biofilm, and alkaline serine protease. A TMT-based quantitative proteomic analysis comparing ΔmicX with the wild-type strain identified 900 differentially expressed proteins, comprising 376 that were upregulated and 524 that were downregulated. The upregulated proteins are primarily associated with porin activity, transmembrane signaling receptor function, and the two-component system. The downregulated proteins are mainly engaged in processes including biofilm formation, cellular communication, and transmembrane transport activity. Of note, the expression levels of proteins involved in the type VI secretion system, exopolysaccharide synthesis, mannose-sensitive hemagglutinin type IV pili (MSHA), and biofilm formation were significantly reduced in the absence of micX. Furthermore, the expression levels of proteins associated with quorum sensing (particularly LuxR and AphA) changed significantly in the ΔmicX vs. WT comparison. These findings strengthened comprehension of the novel sRNA regulatory network and established a theoretical foundation for additional investigations into the virulence of V. alginolyticus. Full article

Biologically controlling Microcystis aeruginosa blooms in saline–alkaline environments remains a major challenge in aquatic ecosystem management. Here, the algicidal performance of an indigenous algicidal bacterium, Bacillus cereus strain PT1 isolated from a sulfate-type saline–alkaline pond, against M. aeruginosa was evaluated, and the underlying metabolic mechanisms were elucidated using non-targeted metabolomics. PT1 exhibited pronounced, stable algicidal activity under saline–alkaline conditions, decreasing the algal cell density from 2 × 10⁶ to 1.25 ± 0.5 × 10⁵ cells mL⁻¹ within 4 days at a rate of 93.75 ± 2.5% (p < 0.05). The above results demonstrate that strain PT1 has a significant lytic effect on M. aeruginosa. Non-targeted liquid chromatography–mass spectrometry analysis identified 298 PT1-induced accumulated metabolic features, and the top 30 candidates comprised organic acids and aromatic compounds, including benzoic acid, coumarin, malonic acid, and signaling-related molecules, including indoleacetaldehyde and nitroprusside. These differential metabolites were associated with algicidal-related pathways, including quorum sensing, two-component systems, ABC transporters, and tryptophan metabolism, outlining a coordinated “regulation–transport–metabolic remodeling” framework. Our findings demonstrate the potential of the indigenous algicidal strain PT1 from saline–alkali ponds to control M. aeruginosa blooms. They also provide an important theoretical basis and data foundation for further elucidating the molecular characteristics of algae solubilizing activity under saline–alkali conditions and developing microbial agents for preventing and controlling Microcystis blooms in saline–alkali ponds. Full article

A high-throughput assay system is developed for measuring communication in microbial biofilms in a 96-well microtiter plate format. In this assay, bioluminescent microbial whole cell biosensor systems (MWCBs) for quorum-sensing molecules (QSMs) are embedded into biofilms, and their response to chemical cues relevant for bacterial communication is assessed. For measuring the response to stress, a sigma factor 54 (σ⁵⁴, RpoN)-dependent MWCB was developed. Biofilms generated in this platform were exposed to gradients of communication signals (QSMs such as N-acetyl-homoserine lactones (AHLs), 3,5- dimethylpyrazin-2-ol (DPO), or phytochemicals that can act as natural quorum-sensing inhibitors (QSIs) such as curcumin or 3,3′-diindolylmethane (DIM)), and the response pattern was monitored. Further, the regulatory role of stressors such as oxidants (H₂O₂) or antibiotics (ciprofloxacin, trimethoprim/sulfamethoxazole) on the communication response is assessed. QSMs induced the MWCBs at 1 h and 4 h in biofilms, but high concentrations inhibited them at 24 h. Curcumin and DIM at higher concentrations lead to inhibition of quorum sensing in biofilms after 4 h and 24 h, but this is not followed by biofilm disintegration. H₂O₂ above 0.002% efficiently inhibited the MWCB activities and led to biofilm disintegration. At lower concentrations of H₂O₂, we observed induction of MWCBs. The antibiotics inhibited the MWCB activity at concentrations above their minimal inhibitory concentration (MIC), but this did not necessarily lead to disintegration of the biofilm. Like low concentrations of H₂O₂, the antibiotics activated the MWCBs at concentrations close to their MIC, possibly as a result of H₂O₂ generated during their bactericidal action. Interestingly, the induction of communication in response to antibiotics can be quenched by iron chelators, suggesting involvement of H₂O₂ and free radicals generated by the Fenton reaction. We hypothesize that the observed response to these stressors reflects increased communication in the biofilm, possibly enhancing tolerance and increasing survival. Full article

Lactic acid bacteria (LAB) are non-spore-forming, non-respiring, Gram-positive cocci or rods that produce lactic acid through carbohydrate fermentation. They are widely used in food and dairy production as probiotics, biofertilizers, and as sources of industrially valuable exopolysaccharides. Growing evidence indicates that many of these functional properties are regulated by quorum sensing (QS), a cell–cell communication mechanism that coordinates bacterial behavior in response to population density. This review summarizes current knowledge on the role of QS in regulating key physiological and functional traits of LAB, including biofilm formation, stress adaptation, metabolite production, and host interactions. Additionally, it highlights the ability of LAB-derived molecules to interfere with QS systems of pathogenic bacteria, contributing to pathogen control. Overall, this review emphasizes QS as a key regulatory mechanism underlying the technological and probiotic potential of LAB, with important implications for food, health, and biotechnological applications. Full article

Yersinia enterocolitica is a foodborne pathogen that forms biofilms on surfaces, enhancing its survivability and increasing bacterial resistance, which poses a significant challenge to public health. Therefore, developing effective strategies to inhibit biofilm formation is crucial. Lipoic acid (LA) is a compound with antibiofilm properties. This study investigates the effects of LA on biofilm formation by Y. enterocolitica BNCC 108930 (a standard strain from the BeNa Culture Collection). Biofilm formation, maturation, removal, and cell viability were evaluated by crystal violet staining, extracellular polysaccharide assay, Methylthiazolyldiphenyl-tetrazolium bromide assays, motility, and quorum sensing (QS) assays. The results indicate that LA interferes with the early stages of biofilm formation by compromising cell membrane integrity and reducing cellular adhesion. Furthermore, 2.5 mg/mL of LA reduced biofilm biomass (with a 48 h treatment inhibition rate of 51.46 ± 1.29%) and extracellular polysaccharide production (with a relative inhibition rate of 30.09 ± 1.8%), while significantly reducing the metabolic activity of bacteria within the biofilm (inhibition rate over 85%) compared to the untreated group. Confocal laser scanning microscopy and field emission gun scanning electron microscopy confirm that LA induces a sparse biofilm structure, reduced aggregation, and decreased biofilm thickness to 21.33 ± 2.27 μm. Motility and QS assays demonstrate that LA affects flagellar motility and the secretion of N-acyl homoserine lactones. Transcriptome analysis revealed downregulation of genes involved in the QS system and biofilm formation (e.g., lsrA, lsrC, lsrD, lsrR, and oppA), as well as upregulation of genes related to bacterial chemotaxis and flagellar assembly (e.g., RS19655, RS15590, fliE, fliJ, fliP, fliA, and fliK). These alterations suggest that LA inhibits Y. enterocolitica biofilm formation by affecting intercellular communication and flagellar motility. This study highlights the antibiofilm properties of LA, providing a theoretical basis for potential applications in microbial and biofilm control. Full article

Achieving completeness of multipartite bacterial genomes has been a difficult task, especially in rhizobia. In this study, we performed a deep bioinformatic analysis of the newly re-sequenced genome of Rhizobium favelukesii LPU83^T. This strain was isolated from acid soils in Argentina and is capable of nodulating several leguminous plants, although it is unable to fix nitrogen efficiently in any of them. Oxford Nanopore sequencing allowed us to completely assemble the symbiotic plasmid of the strain, pRfaLPU83b, and we discovered that it harbors three intact prophages and a high density of insertion sequences (ISs). These characteristics show why it is often so difficult to complete the symbiotic plasmids of rhizobial strains and the importance of having long-read sequencing methods. Upon detailed analysis of this replicon, we identified a complete conjugation system with gene structure consistent with quorum sensing-associated systems that may have contributed to the genetic mosaic structure of the strain. Furthermore, we identified in the symbiotic plasmid of R. favelukesii LPU83^T a large proportion of the symbiotic genes previously identified as essential for Biological Nitrogen Fixation (BNF) in symbiosis with alfalfa, with a high percentage of identity with respect to those of Sinorhizobium meliloti 2011. Among the determinants related to BNF, we found genes encoding the HrrP and SapA peptidases in the LPU83 genome, previously described and related to the degradation of nodule-specific cysteine-rich peptides. These peptides are essential for bacteroid differentiation and, therefore, efficient BNF. Our results show that despite having these genes, they are not directly responsible for the inefficient BNF phenotype of LPU83. Full article

Biofilm production by foodborne pathogens poses significant challenges to food safety and quality, leading to contamination, deterioration, and substantial economic losses for the food industry. Traditional biofilm control methods, such as chemical disinfectants, antibiotics, and preservatives, are sometimes ineffective against persistent biofilms, raising concerns about antimicrobial resistance and the accumulation of chemical residues. Lactic acid bacteria (LAB) have emerged as attractive natural biocontrol agents due to their ability to produce a wide range of antimicrobial secondary metabolites, including bacteriocins, organic acids, hydrogen peroxide, and biosurfactants. This paper thoroughly examines the effect of LAB and their metabolites in preventing and destroying biofilms generated by bacteria relevant to food systems, including Listeria monocytogenes, Salmonella enterica, Escherichia coli, and Pseudomonas spp. The processes causing LAB-mediated biofilm attenuation are thoroughly investigated, including competition for nutrients and adhesion sites, interference with quorum sensing (QS), and metabolic inhibition. Furthermore, recent breakthroughs in LAB-based techniques for food preservation and facility hygiene are discussed, including the creation of LAB-derived antimicrobial coatings, biosurfactant-based cleaning agents, and probiotic bio-coatings for industrial sanitation. The incorporation of nanotechnology has enhanced LAB applications by enabling the creation of LAB-mediated metallic nanoparticles and encapsulated formulations that improve metabolite stability and facilitate controlled release. The combination of LAB metabolites, natural preservatives, and eco-friendly materials in active packaging provides sustainable alternatives to synthetic chemicals. Overall, this review emphasizes the potential of LAB and their bioactive derivatives as environmentally friendly and practical tools for controlling biofilms and preserving food, thereby promoting safer food production systems and accelerating the food industry’s transition to green, sustainable technologies. Full article

Biofilm-associated infections remain a major barrier to wound healing, implant integration, and chronic infection management. Rare-earth oxides (REOs) have emerged as promising antibiofilm materials, though their mechanisms, limitations, and translational potential are still being defined. Cerium oxide (CeO₂) serves as the benchmark due to its redox adaptability, oxygen-vacancy-driven catalytic activity, and host compatibility. In contrast, non-ceria REOs show antibiofilm effects under more restricted conditions, often requiring surface functionalization, composite architectures, or hybrid organic–inorganic interfaces—such as polyphenol coatings or hydroxyapatite-based composites—to achieve comparable activity. Across systems, biofilm control arises not from bactericidal potency but from matrix-level mechanisms including extracellular polymeric substance (EPS) destabilization, extracellular DNA (eDNA) sequestration, redox modulation, and quorum-sensing interference. Preclinical and near-clinical evidence, particularly in chronic wound models, supports the translational relevance of these mechanisms, though the evidence base remains preliminary. This review synthesizes mechanistic data across cerium-, samarium-, lanthanum-, and strontium-based systems to establish a unified framework for REO-mediated biofilm disruption. REOs are positioned as biofilm-modulating platforms that complement antibiotics, enhance healing, and improve outcomes. Design rules emphasize controlled redox activity, targeted coordination chemistry, functional surface engineering, and host-compatible performance, alongside regulatory and manufacturing guidance for future development. Full article

Background/Objectives: Staphylococcus aureus virulence is tightly regulated by the agr (accessory gene regulator) quorum-sensing system. Targeting AgrC, the histidine kinase receptor that serves as a core regulator of agr signaling, represents a promising antivirulence strategy that circumvents conventional bactericidal pressure. Methods: In this study, structure-based virtual screening using AutoDock Vina was performed, followed by molecular dynamics simulations, to identify potent analogs of known AgrC inhibitors. Results: A cyclo[Ala-Phe-OLeu-Phe-D-Leu] exhibiting high binding affinity and stable receptor interaction was selected for further evaluation. Antimicrobial susceptibility testing confirmed that the compound did not inhibit bacterial growth. However, at a concentration of 16 µg/mL, it significantly inhibited hemolytic activity with high reproducibility, and the inhibition rate reached 77.60%. Quantitative reverse transcription PCR (RT-qPCR) demonstrated that the compound decreased some key AgrC-mediated genes, including agrC, agrA, saeS, hla, spa, fnbA, and lukS. Conclusions: These findings identify a promising cyclic pentapeptide inhibitor of AgrC that effectively attenuates S. aureus virulence without exerting bactericidal pressure. This work provides a valuable lead compound and offers novel insights for the development of advanced, safe, and effective antivirulence therapeutics. Full article

Antimicrobial resistance is a critical global health challenge, driven by the rapid emergence of multidrug-resistant bacterial pathogens and exacerbated by extensive antibiotic use, which imposes intense selective pressure and disrupts host-associated microbial communities. In this context, quorum sensing (QS), a conserved molecular communication system that coordinates population-level gene regulation, virulence expression, and biofilm development, has emerged as an attractive target for anti-virulence intervention. A growing body of evidence indicates that phytochemicals, such as curcumin, carvacrol, carnosol, eugenol, and chlorogenic acid, can modulate key QS pathways, including acyl-homoserine lactone-, autoinducing peptide-, and LuxS/AI-2-mediated signaling, thereby attenuating pathogenic behaviors at sub-inhibitory concentrations that do not directly impair bacterial viability. Despite this promise, the translational development of phytochemical-based QS inhibitors remains limited. Because QS also regulates cooperative and homeostatic functions in beneficial bacteria, QS-targeted interventions raise concerns about microbiome disruption and ecological imbalance. Furthermore, the literature is marked by substantial methodological heterogeneity, reliance on indirect phenotypic endpoints, limited molecular target validation, and insufficient assessment of toxicity, bioavailability, and pharmacokinetics. The predominance of simplified in vitro models further constrains extrapolation to complex host-associated and polymicrobial environments. This review critically examines the molecular mechanisms underlying phytochemical modulation of bacterial QS, synthesizes pathogen-focused experimental evidence, and evaluates key translational challenges arising from QS conservation, microbiome considerations, and methodological limitations. Addressing these barriers through mechanism-resolved experimentation, standardized evaluation frameworks, and microbiome-aware testing strategies will be essential for advancing phytochemical QS inhibitors toward clinically and industrially relevant anti-virulence applications. Full article

Pseudomonas aeruginosa biofilm-associated infections present higher recalcitrance to antimicrobial treatments, contributing to persistent and difficult-to-treat infections. Quorum sensing (QS) regulates various cellular processes that are important for the establishment and survival of microbial communities on the host. However, QS inhibitors for the treatment of P. aeruginosa biofilms remain under-researched, partly due to the complexity of QS signalling pathways and the challenge of developing non-toxic inhibitors. Herein, the bioactivity of 2-{(2E)-2-[1-(pyridin-2-yl)ethylidene]hydrazinyl}-1,3-thiazole-4-carboxylic acid (TTNF37), a novel pyridine-based thiazolyl-hydrazone (PTH), was investigated. The compound antimicrobial activity was evaluated against a broad spectrum of microorganisms, its antioxidant potential was assessed using different assays, and its QS-inhibitory effect on P. aeruginosa was studied using bioreporter strains. The effect on P. aeruginosa biofilm formation was analysed in terms of biomass, culturability, and metabolic activity, structure, and cell membrane integrity, while virulence factors were evaluated through absorbance measurements. In addition, molecular docking studies were performed to predict the drug’s interactions with essential QS proteins and biological targets. TTNF37 exhibited potent antimicrobial activity with low to moderate minimum inhibitory concentrations against clinically relevant Gram-negative and Gram-positive bacteria, as well as fungi and yeasts. It also showed antioxidant activity, with variable effectiveness across different radicals and systems. TTNF37 inhibited the 3-oxo-C12-HSL-dependent QS system of P. aeruginosa in a dose-dependent manner, with reductions ranging from 26% to 98%. It also impaired the production and detection of 3-oxo-C12-HSL, resulting in a 56% and 65% decrease in bioluminescence, respectively. Molecular docking studies revealed strong binding interactions with LasI and LasR proteins, with affinity values exceeding those of furvina, a known potent QS inhibitor. Molecular dynamics simulations validated stable TTNF37 binding to LasR and LasI. Both experimental and docking data indicate a significant interaction with human serum albumin (HSA). TTNF37 also significantly reduced pyocyanin production and prevented biofilm set-up with a reduction of 50% in biomass with pronounced alterations in biofilm structure. These results indicate the potential of TTNF37 and related PTHs for treating biofilm-associated infections. Full article

Microbial spoilage and foodborne pathogens remain central challenges in food safety, driven by the metabolic resilience and ecological adaptability of bacteria, yeasts, and molds across diverse food matrices. Active antimicrobial packaging has emerged as a biologically informed strategy that directly targets microbial physiology through controlled release or contact-mediated mechanisms. These systems employ natural antimicrobials, bacteriocins, essential oils, and metal nanoparticles to disrupt cell membranes, inhibit enzymatic pathways, generate reactive oxygen species, or interfere with quorum sensing, resulting in substantial reductions in microorganisms such as Listeria monocytogenes, Salmonella spp., E. coli O157:H7, Pseudomonas spp., Brochothrix thermosphacta, and spoilage fungi. In real food environments, these interventions achieve multi-log reductions and attenuate microbial metabolism, though efficacy varies with pH, water activity, fat content, and storage temperature. Oxygen scavengers further reshape microbial ecology by suppressing aerobic spoilage organisms while inadvertently favoring anaerobic competitors. Despite promising outcomes, concerns regarding nanoparticle migration, microbial resistance potential, and matrix-dependent performance highlight the need for deeper microbiological validation. Future progress will require integrative research linking microbial ecology, packaging material science, and mechanistic toxicology. By aligning with microbial behavior at the cellular and ecosystem levels, active antimicrobial packaging represents a powerful, biologically grounded approach to mitigating foodborne risks. Full article