Search Results (382)

Pseudomonas aeruginosa (PA) is a clinically relevant opportunistic pathogen whose persistence and antimicrobial tolerance are largely driven by biofilm formation and quorum-sensing (QS)-regulated virulence. Targeting QS has therefore emerged as an antivirulence strategy that attenuates pathogenicity without exerting strong selective pressure on bacterial growth. This systematic review (2020–2024) analyzes recent advances in the identification of QS inhibitors against PA, emphasizing studies that integrate in silico approaches. Forty-six studies met the inclusion criteria. All employed molecular docking, and 36.9% (n = 17) incorporated molecular dynamics simulations. While valuable for initial detection, these computational predictions have inherent limitations in accurately estimating binding energy and conformational dynamics, requiring empirical validation to confirm actual biological activity. Approximately one-fifth of the studies were exclusively computational, whereas the remainder combined in silico screening with in vitro and, in some cases, in vivo assays. The most frequently investigated QS regulators were LasR, PqsR, and RhlR, alongside additional virulence-associated proteins. The evaluated compounds encompassed phytochemicals, synthetic molecules, nanomaterials and natural product-derived compounds, several of which demonstrated experimental evidence of biofilm attenuation and reduction in QS-regulated virulence factors. Overall, the findings highlight the value of integrating computational and experimental strategies to rationally prioritize antivirulence candidates. However, the intrinsic complexity and redundancy of the QS network suggest that future research should increasingly focus on multitarget approaches and on the exploration of chemically diverse and previously underexplored compound libraries to improve efficacy against PA biofilms. Full article

Farnesol is a small isoprenoid metabolite that has emerged as a key regulator of fungal biology beyond its original identification as a quorum-sensing molecule in Candida albicans. This review examines farnesol across pathogenic and non-pathogenic fungi, emphasizing its roles in morphogenesis, biofilm development, stress adaptation, membrane-associated physiology, and ecological interaction. In pathogenic fungi, farnesol modulates virulence-related traits, antifungal susceptibility, and host interaction, while in non-pathogenic systems, it influences growth, differentiation, and metabolic balance. Evidence from Saccharomyces cerevisiae, Trichoderma, Candidozyma auris (formerly known as Candida auris), and other fungi highlights the context-dependent nature of its effects. We also discuss farnesol biosynthesis, secretion, and the apparent absence of canonical salvage pathways in fungi. Together, these findings support a broader view of farnesol as a multifunctional fungal metabolite that links signaling with metabolism. Understanding its diverse biological roles may clarify fungal evolution and inform future strategies targeting fungal persistence, adaptation, and antifungal tolerance. Full article

The bacterial Quorum Sensing system refers to the recognition of signaling molecules called autoinducers produced by bacteria when a certain cell density is reached in the environment. Those cell-density-dependent autoinducers regulate and coordinate diverse functional processes, such as bioluminescence, biofilm production, sporulation, and even the expression of some virulence factors, among others. There is a wide variety of autoinducers, and for Gram-negative bacteria, the canonical autoinducers are the N-acyl-homoserine lactones (AI-1). Presently, the production of autoinducers in Leptospira has not been described; therefore, the objective of this study was to detect and identify autoinducers in this bacterial genus. We report here the expression of AI-1 in cultures ≥2.4 × 10⁸ of Leptospira meyeri. Ethyl acetate extracts of Leptospira culture supernatants were capable of activating the β-galactosidase system in the biosensor Agrobacterium tumefaciens strain NTL4. Partial identification of the leptospiral supernatant extracts was done by thin-layer chromatography (TLC), showing a similar retention factor to the synthetic standard N-Octanoyl-DL-homoserine lactone (C8-AHL) in the Leptospira supernatant extracts. In addition, infrared spectroscopy (IR) analysis showed peaks corresponding to the lactone and amide groups in both the C8-AHL standard and the Leptospira meyeri culture extracts. Moreover, High-Performance Liquid Chromatography–Mass Spectrometry (HPLC-MS/MS) confirmed the same retention time (10.7 ± 0.1 min) in both the Leptospira meyeri supernatant extracts and the C8-AHL standard. These results show that Leptospira meyeri synthesizes N-acyl homoserine lactone family autoinducers, particularly the N-Octanoyl-DL-homoserine lactone, and lay the groundwork for future research on Quorum Sensing systems in Leptospira. Full article

Bacillus megaterium isolated from coffee fermentation demonstrated potential probiotic properties against Bacillus cereus ATCC 11778, Escherichia coli ATCC 8739, and Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311 through the production of active compounds, including δ-valerolactam and ε-caprolactam. This is the first report on its potential utility in producing active compounds, forming protective biofilms, or blocking cell adhesion and aggregation of foodborne pathogenic bacteria on material mimicking the intestinal mucosa. The quorum-sensing signal molecule N-butanoyl-L-homoserine lactone, an auto-inducer for biofilm formation, was detected in the crude culture supernatant, supporting its capability for biofilm formation. Characterization assays showed B. megaterium to tolerate up to 6% bile salt and to survive at pH 1.5. In addition, it demonstrated negative hemolytic activity and sensitivity to antibiotics at the level. It also produced various bioactive compounds that function with therapeutic properties. Therefore, B. megaterium has potential to be used as a human and animal probiotic in the future. Full article

Stress-induced perturbations in rumen microbial community structure and function disrupt fermentation homeostasis, consequently impairing production performance and increasing health risks in ruminants. Quorum sensing (QS), a crucial mechanism governing microbial collective behavior and intercellular communication, is increasingly recognized for its role in ecological adaptation of rumen microbiota, yet direct evidence for its regulatory role in the rumen remains limited. This review summarizes the impacts of diverse stressors, including heat stress, cold stress, transport stress, and nutritional stress, on rumen fermentation characteristics and microbial community composition. Building upon this foundation, we discuss the alterations in QS signaling molecules and elucidate underlying microbial adaptation mechanisms from the perspectives of homeostasis disruption, signal transduction, and collective behavior regulation. Although QS-based nutritional and management strategies have shown preliminary potential for alleviating rumen stress, their effectiveness under practical production conditions requires further validation. This review provides a conceptual framework for understanding the potential role of QS in rumen microbial adaptation to environmental and nutritional stress, while highlighting current knowledge gaps and future research directions. Full article

Bacteria in the human intestinal tract express more than 46 million genes, suggesting that interbacterial communication and communication with human cells are well-controlled and synchronized. Many papers have been published on quorum sensing (QS) and other forms of bacterial communication, e.g., nanotubes, nanovibrations, and electromagnetism. Autoinducers (AIs) such as AI-1 N-acyl homoserine lactones (AHLs), AI-2 boron-containing furanosyl borate diesters, AI-3 pyrazinone derivatives, a combination of AI-3/Epi (epinephrine)/NE (norepinephrine), auto-inducer peptides (AIPs), and SdiA (suppressor of division inhibition), along with their receptors, have been well-studied. However, little is known about the roles of quantum mechanics, quantum tunneling, and quantum entanglement in bacterial communication. Most proposals are hypothetical and remain conceptual frameworks supported by indirect evidence rather than validated experiments. The wave-like behavior of ions (quantum tunneling) may facilitate crossing potential energy barriers, such as cell membranes, in concert with protein channels. If this is indeed the case, ions in a quantum-tunneling state would, hypothetically, be able to pass through any part of the cell membrane and cell wall. This would, in theory, enhance biochemical reactions, interbacterial communication, and interactions with human cells. The long-range signaling ability of quanta could allow bacterial cells to maintain contact over long distances, modify their metabolic activities, and activate DNA repair systems. The wave-like behavior of subatomic particles and molecules may cause nanovibrations and generate electromagnetic fields. We argue that electrical signals generated within a biofilm by quanta may attract distant cells and enable cross-species communication. We propose a hypothetical “two-pillar” bacterial communication system, i.e., QS and quantum mechanics/tunneling/entanglement (QMTE), and discuss the advantages of combining both. Full article

Structurally unusual fatty acids (FAs) are biomolecules that connect lipid metabolism, membrane adaptation, and cellular communication. Evidence indicates that FA structural features, including double-bond position, stereochemical configuration, and methyl branches, influence physicochemical properties, metabolic fate, and biological functions. However, these mechanisms have not been systematically integrated. This review summarizes the structural characteristics and biological functions of epoxy, hydroxy, cyclopropane, acetylenic, and conjugated fatty acids. Among these, we focus particularly on structure–function relationships, metabolism of FAs with double bonds in uncommon positions and methyl branches, as these characteristics affect their recognition by metabolic enzymes and metabolic stability. We discuss the metabolic features and biological roles of structurally unusual FAs, with particular emphasis on how structural features regulate unsaturated FA β-oxidation. We clarify how double bonds affect isomerases and reductases through spatial configuration and how methyl branches may alter enzymatic recognition and slow degradation through steric effects. In diffusible signal factor (DSF)-family quorum-sensing signals, double bonds and methyl branches may contribute to the stability and effective concentration of signaling molecules by influencing β-oxidation-related turnover, potentially affecting signal intensity and duration. Overall, this review highlights the role of FA structures in linking metabolism with signal transduction. Future studies integrating biochemical assays, genetic analyses, and multi-omics approaches are needed to elucidate these mechanisms and expand applications. Full article

Phaeomoniella chlamydospora (Pch) is a pioneer pathogen of esca, one of the most destructive grapevine trunk diseases worldwide. A recent work suggests that acetate may act as a quorum-sensing (QS) molecule in Pch, promoting biofilm formation in a concentration-dependent manner. However, the broader influence of acetate on virulence-associated traits remains unexplored. In this study, three Pch isolates were cultured under increasing sodium acetate concentrations (0–100 mM) and assessed for pigmentation, extracellular enzyme activities (amylase, cellulase, protease, esterase, and pectinase), phenolic compound-degrading capacity, and antibacterial activity against a grapevine-associated Pseudomonas sp. isolate. Pigmentation, as well as amylase and cellulase activities, were significantly increased at low acetate supplement levels (6.25–12.5 mM), while esterase activity was unaffected. The expression of these traits decreased above 25 mM acetate supplementation. Phenolic compound degradation capacity, antibacterial efficacy, as well as protease and pectinase activities progressively suppressed at all acetate concentrations. These results indicate that acetate concentration modulates multiple virulence-associated phenotypes of Pch in vitro. Based on these patterns, we propose a hypothetical model in which acetate-dependent phenotypic changes may reflect a shift between establishment-associated activities and reduced extracellular activity at higher acetate levels. This model remains to be validated by mechanistic and in planta infection-based studies. Full article

Nitric oxide (NO) is a small, highly reactive gaseous signaling molecule that plays diverse and context-dependent roles in microbial physiology and host–microbe interactions. Over the past decade, increasing evidence has revealed the dual nature of NO as both an antimicrobial effector and a signaling mediator involved in microbial stress responses, metabolism, biofilm dynamics, quorum sensing, virulence regulation, and symbiotic interactions. In microbial systems, NO influences adaptation to environmental stress and contributes to mechanisms associated with persistence and antimicrobial resistance. In host organisms, NO functions as a key component of innate immunity while also participating in beneficial interactions involving rhizobia, mycorrhizal fungi, and probiotic microorganisms. Despite its biological significance, accurate detection and quantification of NO remain challenging because of its transient nature, high reactivity, low physiological concentrations, and interference from related reactive oxygen and nitrogen species. Recent advances in biosensing technologies have substantially improved NO detection capabilities through the development of electrochemical, optical, enzyme-based, microfluidic, wearable, and implantable sensing platforms. These innovations are complemented by analytical techniques including electron paramagnetic resonance spectroscopy, mass spectrometry, fluorescence-based imaging, and advanced microscopy, which enhance sensitivity, specificity, and spatiotemporal resolution in complex biological environments. Concurrently, statistical and computational approaches—including sensor calibration models, multivariate analyses, machine learning algorithms, and bioinformatics pipelines—have become increasingly important for extracting biologically meaningful information from NO-related datasets. Unlike previous reviews that primarily focus on either NO biology or sensing technologies, this review integrates current knowledge of NO-mediated microbial physiology and host–microbe interactions with recent developments in biosensor engineering, analytical methodologies, statistical frameworks, and emerging artificial intelligence (AI)-driven data interpretation. We further highlight applications of NO detection in infectious disease diagnostics, antimicrobial screening, probiotic and biofertilizer evaluation, environmental microbiome monitoring, and real-time studies of symbiosis and infection. Finally, future directions including miniaturized sensing platforms, multi-omics integration, AI-assisted analytics, and sensor standardization are discussed. By unifying molecular, analytical, and computational perspectives, this review provides a multidisciplinary framework and roadmap for advancing NO-based research and translational applications across microbial, environmental, and host-associated systems. Full article

Foodborne pathogens rely on colonization, biofilm formation, virulence expression, and environmental adaptation as fundamental biological drivers of food safety risk. Quorum sensing (QS), a cell-density-dependent microbial communication mechanism, coordinates the expression of these key phenotypes by integrating intraspecies, interspecies, and host-derived signals, making QS an attractive intervention target in food microbial control. Although QS research has advanced considerably in recent years, existing reviews have largely focused on individual bacterial species or specific classes of signal molecules. A systematic integration of how QS coordinately drives both food spoilage and pathogen virulence remains lacking. In this review, we conceptualize the QS network as a central regulatory hub connecting microbial signal perception to hazardous phenotype expression. We systematically examine the mechanistic roles of QS in food spoilage, biofilm formation, host colonization and invasion, and toxin production. We also summarize current QS-targeted intervention strategies, including inhibition of signal synthesis, enzymatic signal degradation, receptor antagonism, and indirect regulation via beneficial microorganisms. Building on the available evidence, we further analyze the key challenges limiting practical application: signal system specificity, ecological safety, industrial-scale feasibility, and microbial adaptability. Overall, QS-based strategies offer a non-bactericidal route for food microbial control, although substantial barriers remain for translation into complex food matrices. Reframing QS function and intervention from the perspective of food safety risk formation provides an analytical framework that bridges mechanistic understanding with practical application. This framework also establishes a theoretical foundation for developing next-generation food preservation and foodborne disease control strategies. Full article

Background/Objectives: Bitter taste receptors (T2Rs), specifically T2R38, are present in the respiratory epithelium and react with bacterial quorum-sensing molecules to induce an innate immunity response. Although TAS2R38 polymorphisms have been correlated with susceptibility to chronic rhinosinusitis (CRS), they have not yet been explored in odontogenic rhinosinusitis (ORS), a distinct form of CRS with particular microbial and inflammatory features. We aim to establish a proof-of-concept methodology for investigating TAS2R38 genetic variants in ORS using direct maxillary sinus tissue analysis and demonstrate the feasibility of this translational approach. Methods: We conducted a prospective pilot case–control study of 36 ORS patients and 37 controls undergoing septoplasty without sinonasal disease. Maxillary sinus mucosal biopsies were obtained intraoperatively with informed consent. Genomic DNA was extracted using the PureLink Genomic DNA Mini Kit and quantified via NanoDrop spectrophotometry. TAS2R38 haplotypes were determined and classified as taster (PAV/PAV), non-taster (AVI/AVI), or intermediate (PAV/AVI) phenotype. Results: Among fully classifiable canonical TAS2R38 phenotypes (32 ORS patients, 28 controls), distributions were: tasters 12.5% vs. 25.0%, non-tasters 31.3% vs. 25.0%, and intermediate 56.3% vs. 50.0%. AVI/AVI non-taster status was not significantly associated with ORS susceptibility (OR = 1.36, 95% CI: 0.44–4.25; Fisher’s exact p = 0.775). Conclusions: This proof-of-concept study demonstrates that genotyping-grade genomic DNA can be recovered from acutely inflamed maxillary sinus mucosa, validating this substrate for future tissue-based expression, functional, and microbiome analyses not obtainable from peripheral samples; germline genotyping itself does not require sinus tissue. The observed difference in non-taster prevalence (31.3% vs. 25.0%) did not reach statistical significance and is reported descriptively. This directional trend is hypothesis-generating only and, given the limited statistical power, does not constitute evidence for an association. The demonstrated feasibility, together with the established biological rationale, supports an adequately powered confirmatory study and lays the foundation for future investigation of taste receptor genetics in ORS pathogenesis, and potentially personalized therapeutic strategies. Full article

Biofilms are structured communities of microorganisms embedded in a self-produced extracellular polymeric substance (EPS) matrix, whose development significantly enhances microbial resistance to antibiotics, disinfectants, and host immune defenses, posing major challenges in clinical, industrial, and environmental settings. Compared with planktonic cells, biofilm-associated microorganisms can exhibit up to 10- to 1000-fold increased tolerance to antimicrobial agents, contributing to the persistence of biofilm-associated infections (BAIs). These infections remain difficult to eradicate due to reduced penetration, altered metabolic states, and the presence of dormant or persister cells. Anti-biofilm strategies can be broadly classified into physical approaches (e.g., ultrasound, mechanical stress, and light-based approaches) that target biofilm structure; chemical and enzymatic methods (e.g., EPS-degrading enzymes) that destabilize the matrix; and biological and molecular strategies (e.g., quorum-sensing (QS) inhibitors, anti-virulence agents, bacteriophages, phage-derived antimicrobial molecules, antimicrobial peptides, and natural bioactive compounds) that modulate biofilm development and integrity by targeting regulatory pathways and matrix stability through distinct mechanisms of action. Natural compounds, including lactoferrin, lactoferrin-derived peptides, and probiotic and postbiotic fractions of lactic acid bacteria (LAB), as well as plant-derived metabolites, have shown promising anti-biofilm effects, with efficacy often enhanced through complementary or potentially synergistic interactions. However, despite these advancements, clinical translation remains limited. For example, BAIs account for approximately 80% of chronic infections, with high recurrence rates and therapeutic failure reported in device-associated infections and chronic wounds. These limitations highlight the need for clinically translatable, multimodal approaches that integrate structural biofilm disruption, antimicrobial targeting, and host response modulation to design more effective and sustainable anti-biofilm strategies. Full article

Vibrio splendidus is an important opportunistic pathogen that causes diseases in aquatic animals, and its persisters increase the difficulty of aquaculture disease control. The stringent response is a central pathway in bacteria for coping with environmental stress, and the signaling molecule (p)ppGpp, synthesized under the regulation of RelA/SpoT homologs, is closely associated with persister formation and virulence modulation. However, the regulatory mechanisms linking the stringent response to persister formation and virulence in V. splendidus remain unclear. In this study, the core gene deletion strains ΔrelA and ΔrelAΔspoT were constructed via homologous recombination. Combined with D₂O single-cell Raman spectroscopy, transcriptomics, and phenotypic assays, we systematically characterized the biological effects of stringent response inactivation. The results showed that the loss of relA and spoT significantly reduced persister formation and key virulence traits while enhancing biofilm formation. Single-cell Raman spectroscopy analysis indicated that persisters remained metabolically active, accompanied by changes in different cellular components. Transcriptome analysis revealed that the absence of stringent response affected multiple pathways, including ribosomal function, energy metabolism, two-component systems, and quorum sensing. Additionally, the sigma factor RpoS may potentially exert a compensatory function in ΔrelAΔspoT strain, but this requires further validation. In conclusion, the stringent response positively regulates persister formation and virulence in V. splendidus, despite the existence of complex regulatory mechanisms. This study provides a theoretical basis for the development of anti-infective strategies targeting stringent response in aquatic pathogens. Full article

Periodontal disease is a chronic inflammatory condition driven by polymicrobial biofilms whose interaction with the host immune response drives the destruction of tooth-supporting tissues. Within these communities, bacterial cell–cell communication—particularly quorum sensing (QS)—coordinates virulence factor expression, biofilm maturation, and interspecies behaviour, allowing pathogens to mount population-dependent attacks on the host. Disrupting these signals has therefore drawn growing attention as an anti-virulence strategy for biofilm-associated oral infection. Quorum quenching (QQ)—the inhibition or disruption of QS pathways—prevents bacteria from coordinating these virulence-related activities. The candidate inhibitors investigated to date fall into three broad classes: conventional antibiotics used at sub-inhibitory concentrations, plant-derived natural compounds, and synthetic molecules designed to interfere with signal synthesis, signal reception, or signal transduction. In experimental work on periodontal pathogens, agents from each class reduce biofilm formation, suppress virulence factor production, and disrupt microbial communication within polymicrobial biofilms. Clinical translation, however, lags behind the laboratory evidence. Most data still come from in vitro systems and animal models, and the ecological complexity of the oral biofilm makes therapeutic targeting difficult: signals that drive virulence in pathogens also support cooperation among commensals. Toxicity profiles, pharmacokinetics, and well-powered clinical trials are needed before quorum-quenching agents can be considered for routine periodontal care. Even with these caveats, targeting bacterial communication offers a different therapeutic logic from conventional antimicrobials: attenuating virulence rather than killing cells, and so exerting weaker selective pressure for resistance. Further dissection of QS networks in oral biofilms—and the rational design of quenching agents that act on pathogenic rather than commensal signalling—may yield useful adjuncts to current periodontal therapy. Full article

Microorganisms construct complex social communities through the exchange and interaction of chemical substances. Traditional research has typically drawn a strict distinction between quorum-sensing (QS) signaling molecules and cytotoxic secondary metabolites; however, this simplistic classification limits our in-depth understanding of microbial chemical ecology and complex collective behavior. Recent studies have shown that many secondary metabolites exhibit dual functions, acting as signaling molecules that facilitate information exchange at low concentrations. This paper proposes an integrated signaling network framework that views secondary metabolites as key nodes linking microbial collective behavior and environmental adaptation. We explore how this network mechanism overcomes the limitations of linear signaling models, thereby elucidating how microorganisms balance cell growth and metabolite synthesis in dynamic environments. We also introduce emerging spatial omics and synthetic biology tools, which hold great potential for precisely deciphering complex chemical signaling networks at the microscopic scale. Translating these mechanisms into technological applications could enable dynamic, autonomous control of bacterial metabolism in industrial biotechnology, significantly enhancing the yield of target products. Finally, we emphasize the critical importance of reframing chemical ecology as a dynamic signaling network. This shift in ecological and evolutionary perspective not only provides novel intervention pathways based on network decoupling to address the increasingly severe crisis of antibiotic resistance (AMR) but also establishes a theoretical foundation for host microbiome regulation, environmental bioremediation, and industrial multi-strain collaborative engineering. Full article