Search Results (9,861)

Bovine endometritis remains one of the most significant postpartum uterine disorders. It impairs uterine recovery, compromises fertility, and causes substantial economic losses in dairy production. Growing evidence suggests that the disease cannot be attributed solely to postpartum bacterial contamination; rather, it should be understood as a multifactorial failure to restore uterine homeostasis after calving. This review summarises the latest research findings on six interconnected aspects: the clinical significance of postpartum uterine disease; the diagnostic and biological differences between clinical and subclinical endometritis; the role of microbes in the uterus in health and disease; interactions between the host and uterine bacteria; the mechanisms of persistent inflammatory regulation; and current as well as emerging treatment strategies. Current evidence indicates that postpartum uterine disease is more strongly associated with dysbiosis, reduced microbial diversity, and disturbed microbial succession than with the presence of any single pathogen. Disease progression is driven by complex interplay among microbial ligands, epithelial and stromal immune responses, virulence-associated tissue injury, endocrine disruption, and impaired inflammatory resolution. Furthermore, persistent uterine inflammation is regulated by multilayered networks involving cytokines, prostaglandins, noncoding RNAs, extracellular vesicles, metabolic remodeling, and oxidative stress. Although conventional therapies remain relevant in certain clinical cases, microbiota-oriented approaches, particularly probiotic interventions, have emerged as promising adjunctive strategies for the prevention and control of the condition. Overall, bovine endometritis should be viewed as a disorder caused by disrupted interactions between the host, microbiota and inflammation. Future progress will depend on longitudinal, strain-resolved, and function-oriented studies to enable more precise and less antimicrobial-dependent interventions for postpartum uterine health. Full article

Bacterial spot, caused by Xanthomonas species, is a destructive tomato disease that reduces yield and fruit quality worldwide. The tomato resistance gene Rx4 confers hypersensitive response and field resistance to race T3 of Xanthomonas euvesicatoria pv. perforans, but downstream components associated with Rx4-mediated field resistance remain unclear. Here, we compared the susceptible processing tomato line OH 88119 with its near-isogenic line Rx4-1806 after spray inoculation with the race T3 strain Xv829. Transcriptome profiling at 1, 6, and 72 h post-inoculation identified limited transcriptional differences at 1 and 6 h, but 2247 differentially expressed genes at 72 h, including 1712 genes downregulated in Rx4-1806. Enrichment analyses highlighted plant–pathogen interaction, plant hormone signal transduction, and MAPK signaling pathways. Among candidate defense-related genes, SlWRKY33 was downregulated in Rx4-1806 and selected for functional validation. CRISPR/Cas9-mediated knockout of SlWRKY33 enhanced resistance in both OH 88119 and Rx4-1806, whereas SlWRKY33 overexpression increased infected leaf area and bacterial population. Knockout of SlPUB23 enhanced resistance in Rx4-1806 but not in OH 88119. These results suggest that SlWRKY33 and SlPUB23 negatively regulate tomato field resistance to bacterial spot race T3, with SlPUB23 functioning in an Rx4-dependent manner. Full article

HP1090 is a short, cationic, amphipathic peptide derived from scorpion venom and previously described as a membrane-active antiviral compound. Here, we primarily characterize the antiviral activity of HP1090 and assess whether additional antibacterial effects are consistent with membrane-disruptive properties. Chemically synthesized HP1090 exhibited dose-dependent virucidal activity against multiple enveloped viruses, including herpes simplex virus type 1 and 2 (HSV-1, HSV-2), human immunodeficiency virus type 1 (HIV-1), and Zika virus (ZIKV), with IC₅₀ values ranging from 14.7 to 56.1 µg/mL. No activity was observed against the non-enveloped human rhinovirus 14 (HRV14), suggesting strict dependence on a viral lipid envelope. Consistent with a membrane-targeting mechanism, HP1090 induced rapid and concentration-dependent permeabilization of virus-like liposomes. HP1090 also displayed antibacterial activity against selected clinically relevant pathogens in agar-based growth inhibition assays. However, antibacterial effects required substantially higher concentrations (>125 µg/mL) and varied between bacterial species, with some strains showing little or no susceptibility. Membrane permeabilization assays in Listeria monocytogenes demonstrated disruption of bacterial membrane integrity as a contributing mechanism. No cytotoxicity was observed on mammalian cell lines at effective antiviral concentrations. Together, these findings establish HP1090 as a membrane-active venom peptide and, by linking envelope-dependent viral inactivation with bacterial membrane permeabilization, support a shared biophysical mode of action relevant to the development of membrane-targeting anti-infectives. Full article

Lactic acid bacteria (LAB), as important probiotics, face challenges in applications from bacteriophage infection and the instability of foreign genetic elements. Although Gabija systems and their GajA nuclease components have been characterized in model bacteria, their distribution, biochemical properties, and defensive functions in LAB remain largely unexplored. Here, we provide the first systematic characterization of a naturally occurring Gabija system from Ligilactobacillus salivarius Ren and clarify its distribution among LAB. Approximately 9.3% of LAB strains encode the Gabija system, which exists as a gajA-gajB gene cluster. We found that the Gabija system originated independently in different bacterial lineages. The GajA of L. salivarius Ren (LsGajA) was purified and exhibited non-specific nuclease activity that could efficiently cleave various nucleic acid substrates, including plasmids and linear double-stranded DNA (dsDNA). This activity displayed a temperature-dependent profile, with high activity observed from 45 to 60 °C and at pH 8.0. Mg²⁺ markedly enhanced its degradative nuclease activity, whereas high concentrations of dNTPs inhibited DNA cleavage. LsGajA exhibited substrate-dependent differences in cleavage efficiency, indicating that substrate origin and associated physicochemical features may influence its activity. Additionally, we demonstrate that LsGajA exhibits exceptional stability as a nuclease, retaining activity under a wide range of conditions. The LsGabija system significantly enhanced the ability to reject foreign plasmids and provided strong resistance to the bacteriophage T5 in Escherichia coli. This study provides the first systematic biochemical and functional characterization of the Gabija system in LAB, advancing our understanding of this prokaryotic defense system and highlighting its potential for industrial applications. Full article

Urinary tract infections (UTIs) are commonly caused by bacteria that enter through the urethra and multiply in the bladder. The rising antibiotic resistance makes bacterial infections increasingly difficult to treat, necessitating the development of alternative solutions to combat resistant bacteria. The World Health Organization supports the integration of traditional medicine and medicinal plants into health systems, recognizing their therapeutic potential thanks to their active ingredients. In Cameroon, several medicinal plants are traditionally used to treat UTIs. However, information regarding this practice is poorly documented. In fact, systematic lists that would provide a thorough and organized understanding of the use of medicinal plants in treating UTIs are missing. Moreover, there is a lack of scientific evidence for the traditional use of medicinal plants in treating UTIs. This study aims to identify and document medicinal plants that are used to treat urinary tract infections at Dschang and evaluate the antibacterial activity of extracts from the most promising plants against selected bacteria that are responsible for urinary tract infections. The ethnobotanical study was conducted among herbalists, naturopaths, traditional healers and plant users through semi-structured interviews, and the plants listed were identified according to the literature information and at the National Herbarium of Cameroon. Extracts of the most cited plants (10) were obtained by maceration using water or a water–ethanol mixture (3:7; v/v). Then, the antibacterial activity of the as-prepared extracts was evaluated against five bacterial strains responsible for UTIs, such as Escherichia coli ATCC 25922, Staphylococcus aureus HM-468, Pseudomonas aeruginosa NR 48982, Klebsiella pneumoniae NCTCC-13810 and Klebsiella pneumoniae NR 41697, using the microdilution method. A total of forty-one (41) plant species belonging to 26 families were identified as plants used by the respondents to treat urinary tract infections in Dschang. Decoction, infusion and maceration were the most commonly used methods of plant preparation, whereas leaves, bark and fruits were the most used plant organs. From 20 plant extracts tested, the hydroethanolic extracts of Leucaena glauca and Lannea sp. revealed antibacterial activity with MICs ranging from 0.312 to 1.25 mg/mL. The MBC values obtained allowed us to conclude that these extracts exert a bactericidal effect. These results contribute to the identification of plants used to treat UTIs at Dschang and to validate the traditional use of Leucaena glauca and Lannea sp. in the treatment of urinary tract infections. Full article

Background/Objectives: Oral and maxillofacial infections present polybacterial profiles, including both aerobic and anaerobic bacteria. Increasing antibiotic resistance poses a significant challenge to pharmacological treatment of these infections. The aim of this study was to present a bacterial profile and assess antibiotic resistance found in these infections. Methods: This retrospective analysis is based on medical records of 224 patients affected with maxillofacial infections. Microbiological cultures and antibiotic susceptibility testing were performed for all patients. Results: In 78.57% of the patients, a positive microbiological culture was obtained. A total of 72.72% of culture-positive patients showed multi-bacterial cultures (128/176). Predominant bacteria included Streptococcus, detected in 156 cases (39%), followed by Staphylococcus, found in 64 cases (16%), and Prevotella, detected in 56 of 400 total bacterial isolates (14%). The most often isolated aerobic strains were Streptococcus mitis/oralis detected in 64 (16%) cases and Staphylococcus epidermidis detected in 48 cases (12%), while the most common anaerobic strains were Prevotella buccae detected in 14 cases (3.5%). Streptococcus and Staphylococcus exhibited the greatest resistance to clindamycin, accounting for 51.74% and 47.63%, respectively. Aerobic Gram-positive cocci were more resistant to penicillin and amoxicillin than to cephalosporins. Among obligate anaerobes, the lowest antibiotic resistance seen was to metronidazole. The obligate anaerobes except Prevotella were sensitive to clindamycin. Conclusions: A high rate of clindamycin resistance among aerobic and facultatively anaerobic Gram-positive cocci indicates the need to reassess the use of clindamycin in empirical therapy. The bacterial composition of infections suggests the need to use combined antibiotic therapy. First- and second-generation cephalosporins may be an effective alternative to penicillin and its derivatives. Full article

Streptococcus pneumoniae remains a major global health threat and is listed by the World Health Organization as a pathogen in urgent need of new antimicrobial strategies. While primarily considered an extracellular pathogen, S. pneumoniae can persist within splenic macrophages in severe disease, creating a protected intracellular niche that may contribute to fulminant sepsis. We recently demonstrated the concept of an mRNA-based therapeutic approach in which host cells produce the pneumococcal bacteriophage endolysin Cpl-1. Here, we investigated whether expression of Cpl-1 in macrophages can target S. pneumoniae residing within host cells. Using the human THP-1 macrophage line, we demonstrated successful translation and intracellular accumulation of bioactive Cpl-1 following IVT-mRNA transfection. Lysates from Cpl-1 mRNA-transfected cells exhibited bacteriolytic activity, and Western blotting as well as immunofluorescent staining confirmed cytosolic endolysin production. Phagocytosis assays using an encapsulated and unencapsulated pneumococcal strain showed a reduction in intracellular bacterial burden in Cpl-1 mRNA-transfected macrophages compared with control and inactive-mutant Cpl-1 mRNA groups, and a flow cytometry-based assay further corroborated a decreased intracellular bacterial signal. Together, these findings suggest that mRNA-encoded Cpl-1 enhances intracellular killing of S. pneumoniae and supports the feasibility of mRNA-based endolysin therapies to target intracellular pneumococcal reservoirs. Full article

Metronidazole is an antibiotic used to treat Helicobacter pylori, a bacterium responsible for chronic infections in humans that cause gastric inflammation, ulcers, and cancer. However, its long-term administration is limited by toxicity and increased resistance. In the search for more effective agents against H. pylori infection, molecular hybridization has now been applied to the synthesis of the new compound 3. Its structure connects the metronidazole moiety to pectolinarigenin, the latter obtained by acid hydrolysis of glycosylated flavonoids isolated from the plant Linaria reflexa Desf. The NOE effect supported the C-7 functionalization of 3, as evidenced by the energy-minimized DFT-calculated structure. The new molecule enriches the chemical space of known metronidazole–flavonoid analogs, among which the genistein derivative 2 was reported as the most active in inhibiting bacterial strains. The computational analysis of 2 and 3 compared with metronidazole as the reference has provided favorable data for both Absorption, Distribution, Metabolism, and Excretion (ADME) predictions and the probability of anti-H. pylori activity, besides rising docking evaluation on three specific targets and dynamics simulation as inhibitors of the flavodoxin enzyme. The results are promising for further in-depth biological investigation. Full article

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a critical public health threat because infections caused by this pathogen are associated with high morbidity, mortality, and limited effective therapeutic options. Whilst the majority of studies have concentrated on inter-patient bacterial transmission, within-host genomic analysis offers unprecedented resolution for tracking dynamic clone predominance, plasmid rearrangements, and microevolution under clinical selection pressures. Methods and Results: Whole-genome sequencing (WGS) of nine isolates recovered from oral and rectal swabs revealed an exceptional case of CRKP clonal turnover in an intensive care unit (ICU) patient. Three distinct high-risk clones were identified during the 18 days of surveillance: an initial ST101 (Clonal Group (CG) 101) strain (days 1–7) followed by concurrent colonization with ST395 (carrying bla_NDM-5) and ST512 lineages (both CG258, days 11–18). Conclusions: This study describes a rare instance of within-host heterogeneity of CRKP, involving three distinct STs spanning two CGs. Whole-genome analysis revealed potential structural rearrangements of resistance- and virulence-associated plasmids between coexisting lineages. These genomic shifts likely reflect rapid adaptation under the intense selective pressure of broad-spectrum antibiotic therapy, culminating in the persistence of a less virulent yet multidrug-resistant ST512 clone and a favorable clinical outcome with patient recovery. Full article

Probiotic lactic acid bacteria are widely recognized for their health-promoting effects. However, the use of live microorganisms may pose safety concerns and stability limitations. Consequently, postbiotics, defined as inactivated microbial cells and/or their components, have emerged as a promising alternative. This study integrates genome-guided evaluation of probiotic potential, experimental validation of in silico predictions and process optimization for the production of inactivated Lactiplantibacillus plantarum DM1 and KK1 cells as postbiotics. Genome mining identified genes and gene clusters associated with metabolic versatility, antimicrobial activity, gastrointestinal stress tolerance, adhesion and prebiotic substrate utilization. Building on these findings, to generate postbiotics, the efficiency of thermal, enzymatic, mechanical and radiation-based inactivation methods was evaluated in bacterial suspensions prepared in three dairy by-product matrices: milk permeate, sweet whey and sour whey. Complete inactivation of both strain cells was achieved by thermal treatment (3 min pasteurization), γ-irradiation (3 kGy), and combined lysozyme–pasteurization treatment, whereas other treatments showed partial and matrix-dependent effects. Matrix composition significantly influenced treatment efficacy, suggesting a protective role of food components used. These findings highlight the importance of combining genome mining for potential probiotic strain characterization with robust, matrix-adapted inactivation strategies for the development of stable postbiotic formulations. Full article

Hierarchical ZnO–SiO₂/carbon composites (C-Zn1, C-Zn2, C-Zn3) were synthesised via the carbonisation of resorcinol–formaldehyde gels in the presence of ZnO-modified fumed silica, and characterised by N₂ adsorption–desorption, FTIR, XRD, SEM, and zeta potential analysis. The composites exhibited hierarchical micro–mesoporous structures with BET surface areas of 467–499 m² g⁻¹; the non-microporous volume fraction increased from 0.09 (reference carbon RFC, 545 m² g⁻¹) to 0.54–0.63 upon ZnO–SiO₂ incorporation. Adsorption of methylene blue (MB), crystal violet (CV), and rhodamine 6G (R6G) followed the Marczewski–Jaroniec isotherm model. Maximum adsorption capacities for the best-performing composite (C-Zn1) reached 1.22 mmol g⁻¹ for MB, 1.04 mmol g⁻¹ for CV, and 0.63 mmol g⁻¹ for R6G, compared to 1.32, 1.17, and 0.67 mmol g⁻¹ for unmodified RFC. Kinetic analysis revealed up to 3.5-fold faster adsorption rates for C-Zn1 relative to RFC (for CV and R6G), attributed to enhanced diffusion through mesoporous channels while preserving the micropore-driven capacity. Agar well-diffusion assays against four bacterial strains showed no inhibition zones for any composite, indicating that no biologically active concentration of zinc species was released under the assay conditions. The proposed approach yields composites with enhanced adsorption kinetics, preserved capacity, and confirmed non-leaching character, positioning them as effective candidates for water purification. Full article

Considering the therapeutic potential of the Proteus mirabilis PM16 podophage, the interaction between PM16, its host strain, and the mouse immune system was investigated. We evaluated how pre-existing humoral immunity to PM16 influences the immune response against P. mirabilis and the neutralization of the phage itself. Balb/c mice were divided into three groups and immunized two times with (1) 0.9% NaCl, (2) adjuvants, or (3) a mixture of PM16 and an adjuvant. Then, each group was subdivided into three subgroups: mock infection, infection with P. mirabilis, and infection with P. mirabilis followed by model phage therapy with PM16. The obtained results demonstrated that pre-immunization with PM16 enhanced the anti-P. mirabilis IgG antibody response upon bacterial challenge, indicating that the phage potentiates antibacterial immunity. In addition, pre-immunization elicited a significant anti-PM16 antibody response that resulted in in vitro neutralization of phage lytic activity. However, phage-neutralizing antibodies neither decreased the efficacy of phage therapy nor influenced bacteria-specific immune response. Thus, while PM16 can boost the host’s immune response against its bacterial host, the resulting humoral immunity also drives phage clearance through both direct and bacteria-mediated neutralization pathways, revealing a complex immunopharmacological relationship central to phage therapy. Full article

Background: Brucellosis is a global zoonosis caused by Brucella. Histidine biosynthesis is essential for bacterial growth, but its role in Brucella melitensis virulence remains unclear. HisD catalyzes the final two steps of histidine synthesis and is absent in mammals, making it a potential drug target. Results: We constructed a hisD deletion mutant (ΔhisD) and complemented strain (ChisD) via homologous recombination. ΔhisD failed to grow in medium without histidine supplementation. It showed reduced survival under polymyxin B and SDS stress, and impaired outer membrane integrity under polymyxin B challenge, though no defect was observed under non-stressed conditions. Intracellularly, ΔhisD replicated poorly in HeLa and RAW264.7 cells, and this defect was rescued by exogenous histidine. In a mouse model, ΔhisD exhibited lower bacterial loads in liver and spleen, reduced splenomegaly, and attenuated hepatic granuloma formation. Conclusions: Histidine biosynthesis deficiency attenuates Brucella virulence by restricting nutritional acquisition and conditionally compromising outer membrane stability. HisD is a promising target for anti-brucellosis drug development, and ΔhisD holds potential as a live attenuated vaccine candidate. Full article

This study presents an integrated metabolite-centered framework for the comparative evaluation of plant-based substrates through the simultaneous profiling of fermentation-associated short-chain fatty acids (SCFAs) and neuroactive compounds within a single in vitro experimental platform. Unlike conventional studies focusing on individual metabolite classes, the present approach combines in vitro gastrointestinal digestion with simplified bacterial fermentation to characterize substrate-dependent metabolic responses under controlled experimental conditions. Concurrent evaluation of SCFA production and neuroactive compound formation enabled multidimensional assessment of fermentation-associated metabolite profiles and their potential biochemical interrelationships. Significant differences (p < 0.05) were observed among substrates in both SCFA production and neuroactive compound formation. Hemp seed flour exhibited the highest acetate concentration (4.67 mg/100 g) and γ-aminobutyric acid (GABA) level (114.00 µg/g), whereas lentil and corn flour showed elevated propionate levels. Chickpea and bulgur produced the highest butyrate concentrations. Among neuroactive compounds, bulgur exhibited the highest dopamine and serotonin levels, while lentil demonstrated a more balanced metabolite profile. Correlation analysis suggested exploratory associations between SCFA production and neuroactive compound formation. A strong positive correlation between acetate and GABA (r = 0.89) indicated potential co-variation between carbohydrate fermentation and neuroactive metabolite formation, whereas divergent dopamine and serotonin patterns suggested substrate-dependent metabolic differences. Functional mapping further classified substrates into SCFA-oriented, neuroactive compound–dominant, and mixed metabolic profile groups. Collectively, these findings support a metabolite-centered framework for comparative assessment of plant-based substrates based on fermentation-associated metabolite profiles obtained under controlled in vitro conditions. Although the simplified two-strain fermentation model does not reproduce the complexity of the human colonic microbiota, the observed substrate-dependent metabolic differences may provide preliminary insights into biochemical outputs potentially relevant to gut–brain axis-associated pathways. Further studies employing complex microbial communities and in vivo validation are required to confirm the physiological relevance of these findings. Full article

Fruit tree leaves are an abundant agro-waste material with promising yet underexplored biological potential. This study compared the biological activity of aqueous extracts obtained from apple (Malus domestica), apricot (Prunus armeniaca), and cherry (Prunus cerasus) leaves and their kombucha-fermented counterparts in the context of cosmetic and dermatological applications. Phytochemical composition before and after fermentation was analyzed chromatographically. Antioxidant activity was evaluated using DPPH, ABTS, and FRAP assays, while intracellular reactive oxygen species (ROS) levels in keratinocytes and fibroblasts were assessed using the H₂DCFDA probe. Cytotoxicity was determined by Alamar Blue and Neutral Red assays. Antimicrobial activity against seven bacterial strains was investigated using minimum inhibitory concentration and disc diffusion methods. Anti-inflammatory activity was evaluated in LPS-stimulated THP-1 cells by measuring TNF-α, IL-1β, and IL-6 levels using ELISA. The influence of the samples on collagenase, elastase, and hyaluronidase activity was also analyzed. Fermentation increased the content of selected phenolic compounds and enhanced antioxidant, antimicrobial, anti-inflammatory, and anti-ageing properties. Ferments more effectively reduced oxidative stress in skin cells and showed no cytotoxicity within the tested concentration range. These findings indicate that kombucha fermentation may support the valorization of fruit tree leaf agro-waste as multifunctional ingredients for skincare formulations. Full article