Search Results (130)

Toxigenic Klebsiella oxytoca strains linked to antibiotic-associated hemorrhagic colitis produce the cytotoxins tilimycin and tilivalline, which contribute to intestinal epithelial damage during infection. Tilimycin and tilivalline are synthesized by enzymes encoded within the nonribosomal peptide synthetase (NRPS) operon, yet the regulatory mechanisms controlling operon expression remain poorly understood. SdiA, an orphan LuxR-type quorum-sensing regulator, detects exogenous N-acyl homoserine lactones (AHLs) produced by neighboring bacterial species and modulates gene expression in response to interspecies communication. Although SdiA has been implicated in virulence regulation in several enteric pathogens, its role in K. oxytoca remains unclear. This study demonstrates that SdiA positively regulates npsA, the first gene in the NRPS operon, and that this regulatory effect is enhanced in the presence of exogenous AHL. Electrophoretic mobility shift assays indicate that SdiA directly binds to the upstream regulatory region of npsA, supporting a direct interaction consistent with positive transcriptional regulation. Furthermore, deletion of sdiA significantly reduces cytotoxicity toward HeLa cells under the conditions tested. Collectively, these findings identify SdiA as a quorum-sensing-responsive activator of npsA expression and support its role in modulating cytotoxicity in toxigenic K. oxytoca strains. These results provide new insight into the influence of interspecies quorum-sensing signals on virulence-associated regulatory pathways in K. oxytoca. Full article

The clinical effectiveness of clear orthodontic aligners mainly depends on the thermomechanical stability of the polymers in this challenging hydrothermal environment. In this study, we compare the water-induced viscoelastic changes and glass transition temperature (Tg) stability of four polymers with different microarchitectures. Specifically, we examined directly printed photopolymer networks (Tera Harz TC-85 and LuxCreo 4D Aligner), a monolithic thermoplastic (Duran+), and a multilayer thermoplastic (ClearCorrect). Samples were immersed in physiological saline (0.9 wt.% NaCl) at 37 °C for 7 days, and Dynamic Mechanical Analysis (DMA) was performed in three conditions: dry, after immersion, and after a 2 h desorption step, mimicking a typical clinical 22:2 wear cycle. All polymers showed a decrease in Tg after immersion, with TC-85 exhibiting the greatest reduction relative to the dry baseline. Tg recovery after a 2 h ambient desorption step was incomplete and was significantly associated with the amount of water retained after 2 h drying (expressed as % of initial uptake; R² = 0.419), whereas total water absorption after 7 days was not associated with short-term thermal recovery. Full article

Optical-fibre daylighting systems (OFDS) harvest solar energy as a renewable lighting resource by delivering sunlight deep into green buildings. This emerging technology for sustainable infrastructure reduces electric-lighting demand; however, reported performance is difficult to compare across heterogeneous designs, metrics, and validation practices. Therefore, a PRISMA 2020–reported systematic literature review (SLR) of OFDS studies from three databases (Google Scholar, Scopus, and Web of Science; 2000–2025) was conducted, synthesising primary research that quantifies system- or component-level performance, with a focus on (i) plastic optical fibre (POF) transmission characteristics; and (ii) POF-based illuminance model validation. After de-duplication and screening, 106 primary studies were included, and two meta-analyses were performed where data were harmonised from 29 studies in total. Across reported POF configurations, attenuation ranged from 150 to 800 dB/km with a pooled mean of 332.8 dB/km, corresponding to a mean 1 m transmission of 92.7% and median design length scales of ∼3.7 m for 80% transmission and ∼11.6 m to half-power. Across illuminance validation datasets, models showed high linear agreement with experimental measurements (coefficient of determination ($R^2$) = 0.99; slope = 0.99) but typically underpredicted illuminance (geometric mean ratio = 1.16; mean absolute error (MAE) = 27.3 lux; mean absolute percentage error (MAPE) = 17.6%). These findings underscore the need for a standardised evaluation framework, including consistent metric definitions, robust uncertainty reporting, and reusable validation datasets to enable variance-weighted synthesis, while also identifying short-run POF routing as a key lever for improving system efficiency. In addition to providing the OFDS research agenda, this study serves as a roadmap for the industrial development of daylighting systems for green buildings based on harvesting solar energy, with its novelty lying in the PRISMA-guided evidence synthesis and quantitative meta-analytic consolidation of POF transmission and illuminance-validation performance. Full article

Quorum sensing (QS) represents a promising target for anti-virulence therapy; however, effective pharmacological intervention requires a detailed understanding of regulatory network architecture and environmental context. In Klebsiella pneumoniae, the orphan LuxR-type receptor SdiA lacks a cognate LuxI synthase and instead detects exogenous acyl-homoserine lactones (AHLs), positioning it as an inter-species signal integrator. Here, we demonstrate that SdiA functions as a context-dependent regulator whose impact on biofilm formation and virulence gene expression is gated by environmental AHL availability. Using isogenic ΔluxS, ΔsdiA, and ΔluxSΔsdiA mutants in a clinical bloodstream isolate, we show that under AHL-limited conditions, SdiA promotes baseline biofilm development, whereas in the presence of exogenous C6-HSL, it restrains excessive biofilm maturation. Two-way ANOVA confirmed significant genotype, treatment, and interaction effects, establishing that SdiA-mediated regulation is signal contingent. We further investigated the halogenated thiolactone meta-bromo-thiolactone (mBTL), previously described as a QS inhibitor in Pseudomonas aeruginosa. In K. pneumoniae, mBTL acts as a context-selective modulator rather than a simple inhibitor. Under AHL-limited conditions, mBTL phenocopied ΔsdiA, reducing biofilm formation and inducing overlapping transcriptional profiles. In contrast, under AHL-replete conditions, mBTL opposed SdiA-dependent gene expression, consistent with competitive antagonism of ligand-bound receptor. RNA-seq analysis revealed substantial concordance between ΔsdiA and WT + mBTL under AHL-free conditions, with the inversion of transcriptional directionality in the presence of C6-HSL. The findings redefine SdiA as a conditional quorum-sensing integrator and identify mBTL as a ligand-context-dependent modulator of LuxR-type signaling. Our results highlight the necessity of evaluating anti-virulence compounds across relevant signal environments and introduce receptor state-selective modulation as a strategic framework for targeting hybrid quorum-sensing systems in polymicrobial pathogens. Full article

Background: Accurate dietary assessment is vital for preventing malnutrition in aging populations, particularly in home-care settings. Although Large Multimodal Models (LMMs) for nutrient estimation are evolving, their nutrient-specific accuracy requires rigorous validation. Methods: Fifteen standardized hospital meals were photographed under controlled conditions (90-degree angle, 500 lux). Ground truth values were determined by direct weighing. Estimates for energy and macronutrients were performed by 10 registered dietitians (RDs) and 10 AI models (including ChatGPT-4o and Gemini 1.5 Pro). Accuracy was assessed using Pearson’s correlation, Mean Absolute Error (MAE), and Bland–Altman analysis to quantify systematic bias. Results: For energy and carbohydrates, RDs and top-performing AI models (notably ChatGPT-4o and Gemini 1.5 Pro) demonstrated practical accuracy (r > 0.8, frequently within ±10% range). However, accuracy for protein and lipids was significantly lower across all AI models. Specifically, all AI models exhibited a substantial systematic overestimation of lipids (Mean Bias > +20%, p < 0.01), highlighting a critical “invisible nutrient” bias. Conclusions: Current AI tools show potential for caloric and carbohydrate monitoring but struggle with lipid and protein density. These findings emphasize the need for human–AI collaboration (“human-in-the-loop”) and the integration of cooking metadata to improve clinical utility in geriatric nutrition. 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

New N-benzoyl-l-homoserine lactone derivatives bearing a meta-fluorosulfonyl or a meta-methylsulfonyl group have been designed, synthesized and evaluated as quorum sensing (QS) inhibitors. Docking simulations involving the structure of several targeted LuxR-type receptors suggested that a sulfonyl substituent on the benzene ring can trigger interactions within the binding site, possibly consistent with either covalent SuFEx reaction targeting a tyrosine residue or competitive interaction with additional hydrogen bonding. Biological evaluation of the two meta- methyl or fluorosulfonyl-benzoyl acylhomoserine lactone (AHL) analogs as LuxR-regulated quorumsensing inhibitors showed a significant effect for the fluorosulfonyl derivative with an IC₅₀ value of 15 ± 2 µM, while the methylsulfonyl was found to be a weak inhibitor. The stability of the fluorosulfonyl derivative was confirmed by kinetic studies based on ¹⁹F NMR experiments. Investigations dedicated to defining the mechanism of action, either covalent or competitive, were achieved through experiments including inhibition assays without or with pre-incubation in the bacterial medium, and LC/MS analysis with the ExpR protein. The results strongly suggest that the type of inhibition is a competitive one. Full article

Riemerella anatipestifer (R. anatipestifer) is a pathogenic bacterium belonging to the genus Riemerella within the family Flavobacteriaceae, which has multidrug resistance (MDR) and can cause high pathogenicity in waterfowl. The aim of this study was to investigate the antimicrobial resistance and genomic characteristics of R. anatipestifer strains isolated from several regions of China from 2023 to 2024. Two strains were selected for challenge tests, and virulence protection tests were conducted on florfenicol-resistant and florfenicol-sensitive strains. A total of 88 strains of R. anatipestifer were collected from the Shandong, Jiangsu, Guangdong, Hebei and Henan regions. The results showed that the 88 strains included serotypes 1, 2, 5, 6, 7 and 10. Serotype 5 was the most prevalent in the Shandong region. All strains were multidrug-resistant, with the hexaresistance accounting for the highest proportion (42.1%). A total of five resistance genes (tet(X), floR, ermF, qnrS, rmtB) and seven virulence genes were found (ompA, camp, AS87_04050, SIP, Fur, TbdR1, luxE). The challenge test showed that the LD₅₀ of RA12 was 2.75 × 10⁷ CFU/mL, and that of RA26 was 2.57 × 10⁷ CFU/mL. Phylogenetic tree analysis revealed that strain RA26 was closely related to strain 20190403E1-1, and strain RA16 was closely related to strain JW1. In addition, serotypes 2 and 7 identified in this study have been undergoing clonal transmission in China. Virulence protection tests indicated that the results of in vitro drug susceptibility tests were consistent with the therapeutic effects after in vivo treatment, and no R. anatipestifer was found in the visceral tissues of surviving ducklings. This study provides a reference for the rational use of antibiotics. Full article

Artificial cyanobacterial crusts (ACCs) are a potentially effective biological strategy for combating desertification. However, while functional microorganisms influence ACCs formation efficiency, research on their role is limited, and their underlying promotion mechanisms remain unclear. Here, we investigated the effects of three functional synthetic microbial communities (SynComs), each dominated by microorganisms specialized in exopolysaccharide (EPS) production (3 strains), siderophore production (3 strains), or nitrogen fixation (4 strains), on ACCs formation following inoculation with Microcoleus vaginatus. This study was carried out in a controlled laboratory setting with a 12 h light/dark cycle and a light intensity of 2400–2700 lux. Following a 24-day cultivation period, EPS-producing or nitrogen-fixing SynComs significantly increased the chlorophyll-a content by 16.0–16.3%. Except for the nitrogen-fixing bacteria treatment, other SynComs enhanced the soil organic matter content of ACCs by 9.1% to 27.3%. The content of EPS was significantly improved by all three SynComs by 14.1~19.2%. Urease activity rose by 6.7% when siderophore-producing bacteria were added. The impacts of SynComs on ammonium nitrogen (NH₄⁺-N) showed different temporal dynamics: nitrogen-fixing SynComs significantly increased NH₄⁺-N early (≤10 days), while EPS-producing and siderophore-producing SynComs enhanced accumulation later (17–24 days). SynComs inoculation markedly accelerated cyanobacterial and general microbial colonization and growth. In comparison to day 0, the 16S rRNA gene copy number of ACCs increased by 24.1% and 43.0%, respectively, in the EPS-producing and nitrogen-fixing SynComs. Additionally, correlation analysis showed that SynComs transformed the weak correlations in the control into a strong positive correlation between NH₄⁺-N and both Chl-a and microbial biomass. Our findings demonstrate SynComs, particularly the EPS-producing or nitrogen-fixing SynComs, enhance ACCs formation through elucidated mechanisms, providing a theoretical basis for optimizing ACCs-based desertification control strategies. Full article

The greater amberjack (Seriola dumerili) is an economically important marine species that is prone to bacterial infections, resulting in high mortality rates and substantial economic losses. In this study, a virulent bacterial strain, Vh-2, was isolated from diseased greater amberjack and identified as Vibrio harveyi. Experimental infections caused high mortality and severe splenic damage characterized by tissue necrosis, abnormal pigment deposition, cellular disintegration, and extensive immune cell infiltration. A virulence gene analysis revealed that Vh-2 harbored multiple virulence-associated genes such as toxR, toxS, vhpA, vhpB, vhhA, vhhB, luxR, and pap6. Antibiotic susceptibility testing demonstrated ampicillin resistance but sensitivity to ceftriaxone, florfenicol, and meropenem. Transcriptomic profiling of infected spleens identified 396 differentially expressed genes (DEGs) compared to the control group, of which 293 were upregulated and 103 were downregulated. A functional enrichment analysis indicated that these genes were primarily involved in cell cycle regulation, DNA repair, metabolic processes, and immune-related pathways. These findings enhance our understanding of V. harveyi pathogenesis and immune responses of S. dumerili and provide new insights into the prevention and control of V. harveyi infections in marine fish. Full article

Phosphate-solubilizing microorganisms (PSMs) show promise for sustainable agriculture, yet inconsistent field performance limits their application. We investigated phosphate solubilization mechanisms in Enterobacter ludwigii strains GMG278, GMG291, GMG378 and Enterobacter soli GMG1156 through greenhouse wheat experiments, high-performance liquid chromatography (HPLC) organic acid analysis, and comparative genomics. Greenhouse trials demonstrated that bacterial inoculation compensated for phosphorus deficiency, with GMG291, GMG1156, and GMG278 showing superior performance. HPLC identified malic acid as the predominant secreted organic acid, with E. soli producing threefold higher concentrations than E. ludwigii strains. Phosphate solubilization efficiency followed the order FePO₄ > AlPO₄ > Ca₃(PO₄)₂, with maximal release (95.9–97.7 μg/mL) from iron phosphate despite lower malic acid secretion, suggesting siderophore involvement. An inverse correlation between malic acid levels and soluble phosphate concentrations likely reflects competitive bacterial phosphate uptake and secondary precipitation processes. Comparative genomics revealed missense mutations in the LuxR transcriptional regulator of strain GMG378 (Asp86Asn and Arg97Leu) near predicted DNA-binding domains, correlating with reduced solubilization capacity. Phosphate solubilization in Enterobacter proceeds primarily through metal–malic acid complex formation, with strain-specific efficiency linked to LuxR-regulated biofilm formation genes. These findings suggest PSM screening should incorporate biofilm-related genetic markers alongside acid production measurements. Full article

Bacterial blight in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo), poses a serious threat to global rice production. The ability of Xoo to form biofilms is a key factor for its virulence. The OryR protein is a LuxR-type quorum-sensing regulator essential for biofilm formation and Xoo pathogenicity. However, the three-dimensional structure of OryR remains poorly understood. This study integrates homology modeling, molecular dynamics (MD) simulations, and virtual screening to elucidate the structure of OryR and identify potential inhibitors that target its ligand-binding domain. MD simulations confirmed the structural stability of OryR, and comparative analysis with experimentally determined structures of ligand- or inhibitor-bound homologs revealed a binding site in OryR with a distinct hourglass-like shape for long-range contacts. Virtual screening of over 200,000 compounds from four chemical libraries identified several promising inhibitor candidates, with the top compounds showing strong binding energies in both molecular mechanics-generalized Born surface area (−68.3 kcal/mol) and molecular mechanics Poisson–Boltzmann surface area (−19.3 kcal/mol) calculations. Overall, this study provides insights into the OryR structure and highlights potential inhibitors that can be developed as novel agents to control bacterial blight. However, additional experimental validations are required to refine and optimize these leads for drug development. Full article

Visceral white spot disease caused by Pseudomonas plecoglossicida severely threatens marine aquaculture, highlighting the need for effective control strategies. To clarify the role of a novel small RNA, sRNA0024, in bacterial pathogenicity, we constructed an sRNA0024 deletion mutant (ΔsRNA0024) and compared its phenotype and virulence with those of the wild-type strain NZBD9. In vitro assays showed that deletion of sRNA0024 did not affect bacterial growth but significantly reduced biofilm formation and adhesion. In vivo infection experiments in orange-spotted grouper (Epinephelus coioides) demonstrated that the ΔsRNA0024 mutant had a 3.8-fold higher 50% lethal dose (LD₅₀), improved host survival, and milder splenic lesions than the wild type. Histopathology and host transcriptome analyses revealed weakened activation of complement–coagulation cascades, neutrophil extracellular traps, leukocyte migration, and inflammatory signaling pathways, indicating a lower-intensity immune response. Bacterial transcriptomics showed that deletion of sRNA0024 was associated with reduced luxR expression and attenuated quorum-sensing–associated virulence traits, supporting a possible role for this small RNA in modulating luxR expression and QS-related host immunopathology. These findings identify sRNA0024 as an important contributor to the virulence of P. plecoglossicida and highlight the sRNA0024–luxR module as a potential antivirulence target for controlling visceral white spot disease in aquaculture. Full article

The two-component system HPK₆/RRP₆ related to the pln locus of plantaricin biosynthesis was screened out. The overexpression of LuxR-type regulator RRP₆ promoted the transcription of ABC transporter-related genes, thereby increasing plantaricin EF yield. Its yield in 163(rrp₆) reached 16.01 mg/L, which was 1.20-fold that of the original strain. The regulatory mechanism indicated that RRP₆ could bind to two sites of the plnG1 promoter, promoting its transcription and translation, accelerating the secretion of plantaricin and auto-inducing peptide, and enhancing the extracellular plantaricin yield. Amino acids Q73, R144, T171, and Y175 play a crucial role in the binding of RRP₆. Furthermore, potential regulatory compensation within the Lactiplantibacillus plantarum 163 genome may compensate for the negative effects after the deletion of rrp₆. These results provide a novel strategy for increasing plantaricin EF yield, which facilitates its large-scale application as a natural and safe food preservative in agriculture and the food industry. Full article

Oral microbial biofilms play a critical role in the development of various oral infectious diseases, including periodontitis and tooth caries, with Streptococcus mutans recognized as a key biofilm-forming bacterium due to its strong adhesion and acidogenic capacity. Zinc oxide nanoparticles (ZnO NPs) have demonstrated antibacterial properties against various bacteria. This study investigated the antibacterial and antibiofilm properties of ZnO NPs on S. mutans and elucidated their mode of action. Bacterial cultures were exposed to increasing concentrations of ZnO NPs, and planktonic growth, biofilm biomass and biofilm metabolic activity were measured. Complementary assays assessed bacterial ATP content, pH shift in the media, reactive oxygen species (ROS) production, membrane integrity (SYTO 9/PI live/dead staining) and membrane potential. Morphological changes were examined by high-resolution scanning electron microscopy (HR-SEM), while gene expression was analyzed by real-time qPCR. We observed that ZnO NPs inhibited S. mutans growth and biofilm formation in a dose-dependent manner, with both the minimum inhibitory and biofilm inhibitory concentration of 0.5 mg/mL. ZnO NP treatment disrupted bacterial membranes, caused cytoplasmic leakage, and induced ROS production. EPS production determined by Congo Red staining was significantly reduced. Gene expression analysis revealed significant upregulation of vicR, luxS, wapA, gtpB, nox and ftsZ, and downregulation of spaP, gtpC and atpB. In conclusion, ZnO NPs compromise S. mutans viability and biofilm development through oxidative stress and membrane disruption, highlighting their potential use as bioactive materials in oral healthcare. Full article