Search Results (339)

Background: Staphylococcus aureus is a major cause of life-threatening infections, and increasing antimicrobial resistance necessitates alternative therapeutic strategies. This study evaluated the antiquorum sensing and antivirulence activities of selected nonsteroidal anti-inflammatory drugs (NSAIDs) against S. aureus clinical isolates by targeting the accessory gene regulator (agr). Methods: Antimicrobial susceptibility and virulence factor production were evaluated in 56 S. aureus clinical isolates. The MICs of six NSAIDs (Diclofenac, ketoprofen, ketorolac, meloxicam, indomethacin and celecoxib) were determined by broth microdilution, and the effects of sub-MICs (½ and ¼ MIC) on virulence factors were assessed. The expression of agrA, hlb, and hld was analyzed by qRT-PCR, and molecular docking was performed to evaluate interactions with AgrA receptor. Results: Among the isolates, high resistance rates were accompanied with cefoxitin, ceftazidime, and cefepime. Hemolysin, protease, and lipase production were detected in 42.86%, 89.28%, and 94.64% of isolates, respectively. Meloxicam and celecoxib at sub-MIC levels significantly reduced hemolysin, protease, and lipase activities. Additionally, both drugs markedly downregulated agrA expression by 88.9–95.3% and significantly reduced hlb and hld expression by 90.5–99.9% without affecting bacterial growth. Molecular docking demonstrated favorable binding interactions with AgrA. Conclusions: Meloxicam and celecoxib could be promising adjunctive therapies against S. aureus through suppression of the Agr-regulated virulence traits. Full article

Plant-pathogenic bacteria threaten crop productivity and quality, yet chemical options remain limited compared with those for fungal and oomycete diseases. Current management relies mainly on copper bactericides, limited antibiotics, induced-resistance agents, biocontrol and resistant cultivars. However, copper and streptomycin resistance, efflux-mediated multidrug tolerance and rapid pathogen adaptation have weakened these strategies. Target-oriented research provides a framework for exploring agricultural antibacterials, anti-virulence agents, anti-colonization strategies, resistance sensitizers and host-resistance interventions, but many of these approaches remain conceptual, model-system, greenhouse or medical-bacteriology-derived rather than proven field solutions. This review classifies bacterial control targets into two interconnected groups: growth-essential targets, including peptidoglycan biosynthesis, membrane/envelope systems, nucleic-acid processes, protein synthesis, metabolism, nutrient transport and cell division; and anti-virulence/anti-adaptation targets, including secretion systems, quorum sensing, biofilms, motility, adhesion, cell-wall-degrading enzymes, tolerance systems, oxidative-stress responses and host susceptibility factors. Using “Candidatus Liberibacter asiaticus” (CLas) as a case study, genome annotation and infection-stage transcript-abundance data prioritized Sec-dependent secretion, outer-membrane/surface proteins, Bam assembly, nutrient transporters, Clp proteostasis, redox adaptation and core cellular processes as candidate target classes. Envelope-associated, secretion/anti-virulence, nutrient-acquisition and stress-sensitization modules may represent potential directions for downstream validation, but CLas candidates remain hypothesis-generating priorities requiring validation for essentiality, conservation, druggability, delivery feasibility, crop safety and field performance. Full article

The formation of biofilms on medical devices is a major public health challenge, associated with persistent infections, increased antimicrobial resistance and device failure. Biofilms are structured microbial communities, integrated into an extracellular matrix that they produce, giving them protection against antibiotics and host immune defenses. This review provides a synthesis of the mechanisms of biofilm formation, the molecular basis of their resistance, and current and emerging strategies for their prevention and control. This narrative review summarizes (i) the bacterial composition of device-associated biofilms, (ii) the sequential mechanisms of biofilm formation (initial adhesion, maturation, dispersion), (iii) the molecular and physiological basis of biofilm-mediated antimicrobial resistance, and (iv) prevention and control strategies, with particular emphasis on antibacterial and anti-adhesive coatings for orthopedic and dental implants. Surface engineering (anti-adhesive, antimicrobial, nanostructured and biomimetic coatings), anti-biofilm agents (enzymes, quorum sensing inhibitors, bacteriophages), physical approaches (ultrasound, photodynamic therapy) and combined multimodal strategies emerge as the most promising directions. No single strategy ensures complete prevention or eradication of biofilm-associated infections; multidisciplinary multimodal approaches integrating smart biomaterials, controlled antimicrobial release, and artificial intelligence-assisted surface design represent the most realistic clinical pathway forward. Full article

Microbial fermentation of plant-derived materials is increasingly recognized as a strategy to enhance biological activity through phytochemical bioconversion. In this study, we investigated the antibiofilm effects of fermented Zingiber officinale rhizome extract against major periodontal pathogens and examined the underlying mechanisms. Ginger extract fermented with plant-derived lactic acid bacteria showed significantly greater inhibition of biofilm formation by Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans than non-fermented extract. The inhibitory activity increased with fermentation time, resulting in approximately 60–70% reduction in biofilm formation at higher concentrations. Chromatographic analysis revealed decreased 6-gingerol and increased 6-shogaol levels after fermentation, suggesting bioconversion of 6-gingerol to 6-shogaol. Direct treatment with 6-shogaol inhibited biofilm formation in a dose-dependent manner in all tested pathogens. Quantitative PCR analysis further showed that 6-shogaol significantly downregulated the quorum sensing-related gene luxS and multiple adhesion- and virulence-associated genes, including flp, fimA, mfa1, radD, fadA, ltxA, and rgpB. These findings indicate that lactic acid bacterial fermentation enhances the antibiofilm activity of ginger extract through increased 6-shogaol production, highlighting its potential as a natural anti-biofilm and anti-virulence agent for periodontal disease prevention and management. Full article

Lactic acid bacteria (LAB), particularly members of the genus Lactobacillus, have emerged as promising biological agents with antimicrobial and anti-biofilm properties. While numerous individual studies have reported their inhibitory effects against pathogenic microorganisms, a systematic understanding that integrates their functional components, molecular mechanisms, and material-based applications remains lacking. In this review, we provide a comprehensive and component-oriented overview of LAB-mediated antimicrobial strategies. We first summarize secreted factors, including organic acids, bacteriocins, hydrogen peroxide, and extracellular vesicles, which collectively contribute to direct pathogen inhibition and environmental modulation. We then discuss cell-associated components such as surface-layer proteins and exopolysaccharides, highlighting their roles in adhesion interference and competitive exclusion. In addition, we examine whole-cell effects, including niche competition, quorum sensing disruption, and host immune modulation. Importantly, we place particular emphasis on the anti-biofilm activity of lactobacilli, detailing mechanisms involved in the prevention of the pathogen initial adhesion, disruption of extracellular polymeric substance matrices, and destabilization of mature biofilms. Finally, we explore emerging strategies that integrate lactobacilli with biomaterials, particularly hydrogel-based systems, to achieve controlled delivery, enhanced stability, and sustained antimicrobial activity. These biohybrid approaches represent a promising direction for the development of next-generation antimicrobial materials. These findings support the concept of LAB-based living antimicrobial materials as a next-generation strategy to combat biofilm-associated infections. Overall, this review aims to bridge the gap between molecular functions and translational applications of lactobacilli, providing new insights into its potential as a versatile platform for antimicrobial and anti-biofilm interventions. Full article

Serratia marcescens has emerged as an important opportunistic pathogen in intensive care units (ICUs), where critically ill patients, invasive devices, antimicrobial exposure, and complex environmental reservoirs create favorable conditions for colonization, infection, and recurrent outbreaks. This narrative review synthesizes evidence from the past decade regarding the clinical and molecular epidemiology, environmental persistence, device-associated transmission, biofilm-mediated resistance, and infection-control strategies of S. marcescens in ICU settings. The literature was reviewed using an integrative approach informed by Ferrari’s narrative review framework, with thematic synthesis across clinical, microbiological, environmental, and genomic domains. Recent evidence indicates that ICU-associated S. marcescens infections frequently involve respiratory tract colonization, ventilator-associated pneumonia, bloodstream infection, urinary tract infection, and device-related transmission. Hospital water systems, sink drains, wet surfaces, ventilator circuits, reusable equipment, and contaminated antiseptic or liquid products may serve as persistent reservoirs, particularly when biofilm formation supports long-term survival and recurrent dissemination. At the molecular level, S. marcescens demonstrates substantial genomic diversity, intrinsic and acquired antimicrobial resistance, inducible AmpC β-lactamase activity, efflux-mediated tolerance, and plasmid-associated resistance gene transfer. This review particularly emphasizes the molecular determinants that enable S. marcescens to persist in ICU ecosystems, including AmpC-mediated β-lactam resistance, efflux-associated tolerance, quorum-sensing-regulated biofilm formation, plasmid-mediated horizontal gene transfer, and WGS-defined clonal transmission. Whole-genome sequencing, rapid molecular diagnostics, active surveillance, environmental sampling, and integrated infection-control bundles have become increasingly important for distinguishing clonal outbreaks from endemic transmission and guiding timely interventions. Emerging perspectives emphasize the need to combine antimicrobial stewardship, environmental engineering, respiratory-care auditing, anti-biofilm strategies, and AI-assisted real-time surveillance into adaptive ICU infection-control frameworks. Overall, S. marcescens should be regarded not merely as an episodic outbreak organism, but as a highly adaptable ICU-associated pathogen requiring multidisciplinary prevention strategies. Full article

Background: The World Health Organization has identified the growing ineffectiveness of antibiotics against resistant pathogens as a global threat to public health, linked to increased morbidity and mortality. In this context, Pseudomonas aeruginosa stands out as a multidrug-resistant, biofilm-forming pathogen whose biofilm formation increases its tolerance to antimicrobials, which has driven the development of anti-virulence strategies as a therapeutic alternative. In this regard, the present study aimed to evaluate extracts and compounds from Piper species in assays targeting the inhibition of biofilm and virulence factors in Pseudomonas aeruginosa, as well as their anti-quorum sensing activity using Chromobacterium violaceum as a biosensor model. Methods: For this purpose, quorum sensing interference was first assessed through inhibition of violacein production using C. violaceum ATCC 12472 as a biosensor model. The modulation of virulence-associated phenotypes in P. aeruginosa ATCC BAA-47 was subsequently examined through inhibition of biofilm formation by crystal violet staining and spectrophotometric quantification of elastase, protease and pyocyanin production. Results: It was found that extracts from P. aduncum, P. sucrense, P. grande, and P. cumanense inhibited biofilm formation in P. aeruginosa and showed potential activity against quorum sensing in the C. violaceum model, while P. ceanothifolium exhibited only antibiofilm activity. Furthermore, hydroquinone-type compounds and benzoic acid derivatives reduced biofilm formation and virulence factors in P. aeruginosa. Conclusions: The results obtained demonstrate antibiofilm and anti-virulence activity, as well as a possible modulation of quorum sensing in model systems, suggesting that Piper species represent a promising source of bioactive compounds. Full article

Background/Objectives: Numerous natural compounds have been reported to exhibit anti-virulence properties against pathogenic bacteria. Particularly, plants constitute a rich source of anti-quorum-sensing (QS) and anti-biofilm compounds with highly diverse chemical structures. Notably, several studies reported that plant-derived pentacyclic triterpenoids exert anti-biofilm activity against Pseudomonas aeruginosa without affecting bacterial viability, suggesting that this class of naturally occurring chemical compounds may represent a source of potent and clinically relevant anti-biofilm agents. Methods: To further investigate this hypothesis, we evaluated several commercially available pentacyclic triterpenoid acids of the oleanane, ursane and lupane types for their potential impact on QS mechanisms and biofilm formation in the P. aeruginosa PAO1 model strain. Results: Oleanane-type (oleanolic acid and maslinic acid), ursane-type (ursolic acid and corosolic acid) and lupane-type (betulinic acid) triterpenoids inhibited the expression of the QS-regulated lasB and rhlA genes as well as biofilm formation, without affecting bacterial growth. Among tested compounds, oleanolic and ursolic acids, at 400 µM, exhibited the strongest anti-biofilm activities, with 45% and 40% inhibition, respectively. Fluorescence microscopy revealed a marked disorganization of biofilm architectures, with bacterial communities failing to establish compact cell-to-cell attachment and confluent microcolonies. Further analyses indicated that these triterpenoid acids did not affect the expression of QS-regulator genes (lasR/I and rhlR/I), suggesting that their impact on lasB and rhlA expression and biofilm formation is independent of the las and rhl systems. Conclusions: These findings suggest that oleanane and ursane triterpenoid acids represent promising chemical backbones for the development of strategies aimed at inhibiting P. aeruginosa biofilm formation. 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

Pseudomonas aeruginosa, an opportunistic pathogen, is a major threat to hospital infection control and global public health due to its strong environmental adaptability, complex virulence systems, efficient biofilm formation capability, and widespread multidrug resistance. Traditional single-target antibiotics are often inadequate for clinical treatment. The research into Plant-Derived Bioactive Compounds for combating P. aeruginosa infections is reviewed, highlighting their advantages (many of which are extensively studied in Traditional Chinese Medicine) over conventional antibiotics. The antimicrobial mechanisms of these compounds include the inhibition of bacterial quorum sensing (QS) systems to suppress virulence factor expression rather than direct anti-bactericidal effects, delaying the development of resistance. The abundant natural medicinal plants and their diverse chemical structures provide ample material for active compound screening to identify unique chemical compositions with specific binding to pathogen targets. Plant-Derived Bioactive Compounds exhibit excellent safety profiles, targeting bacterial-specific pathways or host immune regulation, resulting in minimal off-target toxicity. Plant-Derived Bioactive Compounds exert anti-P. aeruginosa effects via inhibition of QS systems to reduce pathogenicity by disrupting intercellular signaling, suppressing biofilm formation/maturity to overcome biofilm-associated resistance, directly interacting with bacterial structure. Plant-Derived Bioactive Compounds are promising treatments for drug-resistant P. aeruginosa infections, providing lead compounds for novel anti-infective drug development. 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

Antimicrobial resistance (AMR) is one of the most serious threats to global public health, driven in part by extensive antibiotic use in food-producing animals. The poultry industry, a major contributor to the global animal protein supply, has depended on antibiotics for growth promotion and disease control, thereby contributing to the emergence and dissemination of AMR zoonotic bacteria. This review synthesizes current evidence on the potential of phytochemicals (PCs), plant-derived bioactive compounds, as sustainable non-antibiotic alternatives for controlling bacterial foodborne pathogens in poultry. Relevant literature including in vitro and in vivo studies assessing PCs against major poultry-associated zoonotic bacteria, including Salmonella enterica, Campylobacter spp., Clostridium perfringens, Listeria monocytogenes, and pathogenic Escherichia coli, is examined. Evidence indicates that PCs exert antimicrobial and anti-virulence effects through mechanisms like bacterial membrane disruption, inhibition of quorum sensing and virulence gene expression, modulation of gut microbiota, and enhancement of host immune responses. In vivo studies demonstrate reductions in pathogen colonization and improvements in gut health and performance metrics in poultry. Despite these promising findings, challenges remain in bioavailability, dose optimization, standardization, and regulatory approval. Overall, PCs represent a promising component of integrated antimicrobial stewardship strategies in poultry production, with significant implications for mitigating zoonotic AMR transmission. 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

Chronic and infected wounds remain difficult to treat due to persistent microbial burden, biofilm formation, and dysregulated inflammation. As a multifunctional polyphenol, curcumin exhibits broad-spectrum antimicrobial, anti-inflammatory, and antioxidant activities. Nevertheless, the clinical application of curcumin is constrained by its limited solubility in water, inherent instability, and insufficient bioavailability. Chitosan, a cationic polysaccharide, provides complementary advantages including intrinsic antimicrobial activity, mucoadhesion, and the capacity to form versatile delivery platforms such as nanoparticles, hydrogels, and films. This review reframes chitosan–curcumin systems as dual-function bioactive platforms in which both the carrier and payload actively contribute to therapeutic outcomes. Mechanistically, chitosan disrupts microbial membranes, enhances bioadhesion, and supports tissue regeneration, while curcumin modulates intracellular targets including reactive oxygen species, quorum sensing, and inflammatory signaling pathways. Their integration enables multimodal antimicrobial activity, improved biofilm disruption, and coordinated regulation of the wound-healing cascade. This review critically examines the structure–function relationships governing release kinetics, stability, and cytocompatibility, with particular emphasis on chitosan molecular weight, degree of deacetylation, crosslinking strategies, and curcumin loading. Solubility-enhancement strategies for curcumin, including surfactants, nanoparticles, solid dispersions, and chemical derivatives, are evaluated in the context of antimicrobial efficacy and cytotoxicity. Finally, the review highlights translational challenges and future directions, such as antibiotic synergy, antifungal applications, formulation complexity, and the emerging role of artificial intelligence in predictive material design. Collectively, these insights establish design principles for next-generation multifunctional biomaterials that integrate antimicrobial activity with immune modulation and tissue repair. Full article

Biofilm formation constitutes a major factor in antibiotic treatment failure, shielding bacteria from drugs and promoting persistence. This study demonstrates that the anti-biofilm action of clove oil enhances the efficacy of fosfomycin against Escherichia coli O157:H7 (E. coli O157). Using a luxS-eGFP reporter system, it was found that clove oil inhibited E. coli O157 biofilm formation by up to 80% via suppression of the LuxS/AI-2 quorum sensing (QS) system and bacterial motility. Crucially, this disruption was shown to correlate with a strong synergistic effect when combined with fosfomycin in vitro. In a murine peritoneal infection model, the combination therapy demonstrated superior efficacy compared to monotherapy. Specifically, bacterial loads in the liver, spleen, and small intestine were significantly reduced, and histopathological damage was alleviated. Mechanistically, these effects were linked to the downregulation of the QS. These findings indicate that clove oil acts as a potent adjuvant to fosfomycin by disrupting biofilms, offering a promising strategy against systemic infections caused by E. coli O157. Full article