Search Results (2,165)

Trichomoniasis is the most prevalent non-viral sexually transmitted infection worldwide and is caused by Trichomonas vaginalis. The development of resistance against the standard treatment, metronidazole, highlights the need for alternative therapeutic approaches. The role of innate immune cells is crucial for understanding trichomoniasis; however, the contribution of monocytes remains poorly characterized. We previously reported that the antimicrobial peptides LL-37 and its derivative KR-20 are trichomonacidal. In other systems, LL-37 displays immunomodulatory effects. Nevertheless, whether these peptides modulate monocyte responses in the presence of T. vaginalis remains unknown, which was the aim of this study. U937 monocytes were co-incubated with LL-37 or KR-20 (3 h), with or without parasite. Monocyte metabolic activity, nitric oxide production, and relative expression of innate immune genes were assessed. LL-37 decreased monocyte metabolic activity and upregulated TNF-α expression (10 and 5 μM, respectively) in parasite-challenged monocytes. Meanwhile, KR-20 (2.5–10 μM) preserved metabolic activity, bound microbial components (LPS), reduced parasite-induced nitric oxide production, and downregulated the expression of IL-8, TNF-α, IL-1β, and COX-2 in infected monocytes. This work provides initial evidence that KR-20 modulates innate immune response in monocytes during T. vaginalis infection, suggesting its potential—yet to be fully validated—as an immunomodulatory candidate for trichomoniasis. Full article

Background/Objectives: Bacterial outer membrane vesicles (OMVs) play a role in bacterial communication, virulence, antimicrobial resistance, and host–pathogen interaction. OMV isolation is a key step for studying these particles’ functions; nevertheless, isolation procedures can greatly influence the yield, purity, and structural integrity of OMVs, thereby affecting downstream biological analyses and functional interpretation. Methods: In this study, we compared the efficacy of two OMV isolation techniques, differential ultracentrifugation (dUC) and size-exclusion chromatography (SEC), in separating and concentrating vesicles produced by two Escherichia coli strains belonging to uropathogenic (UPEC) and Shiga toxin-producing (STEC) pathotypes. The isolated OMVs were characterized using a multi-analytical approach including transmission and scanning electron microscopy (TEM, SEM), nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), ζ-potential measurement, and protein quantification to assess the purity of the preparations. Results: Samples obtained by dUC exhibited higher total protein content, broader particle size distributions, and more pronounced contamination by non-vesicular material. In contrast, SEC yielded morphologically homogeneous and structurally well-preserved vesicles, higher particle-to-protein ratios, and lower total protein content, reflecting reduced co-isolation of protein aggregates. NTA and DLS analyses revealed polydisperse populations in samples obtained with both isolation methods, with DLS measurements highlighting the contribution of larger or transient aggregates. ζ-potential values were close to neutrality for all samples, consistent with limited electrostatic repulsion and with the aggregation tendencies observed in some preparations. Conclusions: This study describes features of OMV produced by two relevant E. coli strains considering two isolation strategies which exert method- and strain-dependent effects on vesicle properties, including size distribution and surface charge, and emphasizes the trade-offs between yield, purity, and vesicle integrity. Full article

Due to the indiscriminate use of antimicrobial drugs in the treatment of infectious diseases, human pathogenic bacteria have developed resistance to many commercially available antibiotics. Medicinal plants such as Convolvulus arvensis represent a renewable resource for the development of alternative therapeutic agents. This study aimed to evaluate the antibacterial activity of silver nanoparticles (AgNPs) biosynthesized from C. arvensis against two clinical antibiotic-resistant bacterial isolates. The pathogenic isolates were identified as Staphylococcus aureus MRSA and Escherichia coli ESBL using 16S rRNA gene sequencing. Silver nanoparticles were synthesized via a green synthesis approach, and their physicochemical properties were characterized using UV–Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, zeta potential, and dynamic light scattering (DLS). The synthesized C. arvensis–AgNPs exhibited a surface plasmon resonance peak at 475 nm and predominantly spherical morphology with particle sizes ranging from 102.34 to 210.82 nm. FTIR analysis indicated the presence of O–H, C–O, C–N, C–H, and amide functional groups. The nanoparticles showed a zeta potential of −18.9 mV and an average hydrodynamic diameter of 63 nm. The antibacterial activity of the biosynthesized AgNPs was evaluated against methicillin-resistant S. aureus (MRSA and ATCC 29213) and E. coli (ESBL and ATCC 25922) using agar diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. Inhibition zones ranged from 10 to 13 mm, with MIC and MBC values of 12.5–25 µg/mL and 25–50 µg/mL, respectively. In addition, the nanoparticles exhibited antioxidant activity (DPPH assay, IC₅₀ = 0.71 mg/mL) and anti-inflammatory effects as determined by protein denaturation inhibition. No cytotoxic effects were observed in the MCF-7 cell line at the MIC level. These findings suggest that C. arvensis–AgNPs have potential as natural antimicrobial, antioxidant, and anti-inflammatory agents. Full article

Hop (Humulus lupulus L.) is recognized as a valuable source of bioactive compounds; however, the phytochemical composition and biological potential of wild Romanian hops remain insufficiently characterized. In this study, the bioactive profile of wild hop cones was evaluated using an integrated phytochemical, biological, and in silico approach. The hydroethanolic extract was characterized by a total phenolic content of 25.61 mg GAE/g DW and a total flavonoid content of 3.20 mg RE/g DW, with α-acids predominating (8.77%) and β-acids detected only at trace levels (0.15%). Hydrodistillation yielded 0.613 ± 0.11% essential oil, which was rich in sesquiterpene hydrocarbons (64.61%), mainly α-humulene, β-caryophyllene oxide, selina-3,7-diene, and germacrene B. The hydroethanolic extract exhibited strong antioxidant activity (IC₅₀ = 5.03 µg GAE/mL), whereas the essential oil showed a moderate but dose-dependent radical-scavenging capacity (IC₅₀ = 0.44% v/v). In addition, the essential oil displayed pronounced antibacterial and antibiofilm activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, at 25 mg/mL, with the highest antibiofilm inhibition observed for Pseudomonas aeruginosa (96.44%). Molecular docking analysis suggested that the major volatile constituents may interact with Staphylococcus aureus Sortase A, providing a plausible mechanistic basis for the observed antibiofilm effects. Overall, these findings indicate that wild Romanian hop cones represent a promising source of antioxidant and antimicrobial bioactive compounds, supporting their potential applications in pharmaceutical, food, and cosmetic formulations, as well as in natural-product-based drug discovery. Full article

Rosacea is a chronic inflammatory skin disorder characterized by oxidative stress, innate immune dysregulation, vascular instability, and microbiome-related triggers. Glycyrrhiza glabra (Gg, licorice) root contains phenolics and triterpenoids with antioxidant, anti-inflammatory, antimicrobial, and anti-angiogenic properties that may benefit rosacea-prone skin. Xanthan-gum hydrogels containing 2% methanolic Gg extract (S1, S2) were prepared and characterized. Rheology, in vitro release, and in vitro permeation were evaluated, with the aim of assessing their suitability as topical formulations for rosacea-prone skin. Antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. Antimicrobial effects were tested against S. pyogenes, S. aureus, and C. acnes. Safety and bioactivity were examined through HaCaT keratinocyte assays (MTT, Neutral Red, LDH), the HET-CAM irritation test, and the CAM angiogenesis assay. Immunocytochemistry was performed on rosacea-related inflammatory markers. Both hydrogels showed suitable rheology, sustained release, and preserved strong antioxidant activity. Moderate antimicrobial effects were observed, particularly against S. pyogenes and C. acnes. HaCaT cell viability remained above 84% for the S2 formulation at the highest concentration (200 µg/mL), indicating improved cytocompatibility compared with formulation S1. The hydrogels were non-irritant in the HET-CAM model and reduced neovascularization in the CAM assay, with a more sustained effect observed for formulation S2. Immunohistochemistry supported potential modulation of inflammatory pathways relevant to rosacea, evidencing suppressed VEGF expression and preserved CD44-mediated integrity, particularly in the Labrasol-based formulation (S2), while Caspase-3 staining indicated a controlled apoptotic profile. Overall, Gg hydrogels are safe, biocompatible, non-irritant, and exhibit antioxidant, antimicrobial, and anti-angiogenic activities, supporting their potential as biocompatible topical formulations with antioxidant and pathway-modulating properties relevant to the biological features associated with rosacea, while underscoring the importance of formulation design. Full article

This study investigated the phytochemical composition and biological activity of Cymbopogon citratus microshoot cultures and evaluated their suitability for incorporation into a cosmetic formulation. Microshoot cultures were established on Murashige and Skoog media supplemented with plant growth regulators and served as a reproducible source of biomass. Methanolic and ethanolic extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Chemical composition was characterized using LC-MS/MS analysis, which revealed the presence of phenolic acids and flavonoids, with p-coumaric, caffeic, and ferulic acids being among the most abundant detected constituents. In biological assays, the extracts inhibited murine tyrosinase in a concentration-dependent manner and exhibited antimicrobial activity against selected oral and skin-associated microorganisms, including Streptococcus mutans, Streptococcus pyogenes, and Staphylococcus epidermidis, as well as showing fungistatic and fungicidal effects against Candida albicans. Cytotoxicity analysis performed on HaCaT keratinocytes confirmed biocompatibility within the tested concentration range. To assess formulation suitability, the microshoot extract was incorporated into an oil-in-water (O/W) cream, which maintained stable pH, viscosity, and physical properties while preserving the antioxidant activity of the extract. Overall, these findings indicate that C. citratus microshoot cultures represent a reproducible source of bioactive metabolites with potential application in cosmetic formulations. Full article

This review focuses on the research progress on natural products as β-lactam antibiotic adjuvants, aiming to address the escalating challenge of antibiotic resistance, particularly the inactivation of antibiotics caused by β-lactamases. The article provides an in-depth analysis of the mechanisms by which plant-derived (e.g., flavonoids, tannins, phenolics, terpenoids, and alkaloids) and microbial-derived (e.g., clavulanic acid, fungal metabolites, bacteriophages) natural products enhance antimicrobial efficacy. Key potentiation strategies discussed include efflux pump inhibition, membrane permeability alteration, biofilm disruption, PBP2a inhibition, and direct β-lactamase inhibition. Additionally, the review outlines in vitro methods (e.g., dilution and checkerboard assays) and in vivo models (e.g., mouse infection models) used to assess synergistic effects. It also addresses major challenges in identifying active compounds, elucidating mechanisms of action, and pharmacokinetic characterization. Looking forward, the article highlights the potential of multi-omics approaches, artificial intelligence, and nanotechnology to overcome existing bottlenecks, providing novel strategies for the development of effective and safe antibiotic adjuvants. These advances are expected to provide both theoretical insights and practical guidance for combating antibiotic-resistant bacterial infections. Full article

This study aimed to design a new composite with promising antimicrobial and antioxidant properties by a simple modification process of natural bentonite (B) with polysaccharide chitosan isolated from edible mushrooms Agaricus bisporus—ChM (sample B–ChM) and subsequently with a cationic surfactant—hexadecyltrimethylammonium bromide—HB (sample B–ChM–HB) for effective removal of mycotoxin zearalenone (ZEN). Characterization confirmed the presence of ChM in B–ChM and both ChM and HB in B–ChM–HB. Compared to non- or slightly inhibitory activity of B and B–ChM, B–ChM–HB showed fungicidal activity against yeast Candida albicans and mycotoxigenic mold Aspergillus flavus, with a reduction of 6.00 log10 (CFU/mL) and 5.32 log10 (CFU/mL), respectively. B–ChM–HB showed a very high neutralization ability on •DPPH (89.03%–95.99%) in the concentration range of 0.625–5.0 mg/mL, the highest ferrous ion chelating ability (80.25%) at a concentration of 0.625 mg/mL, and did not induce lipid peroxidation in the linoleic acid model system. While B and B–ChM exhibited low adsorption of ZEN, its adsorption by B–ChM–HB was significantly higher. The equilibrium results of B–ChM–HB for ZEN were in accordance with the linear isotherm model at pH 3 and 7, pointing out that hydrophobic interactions (partitioning process) were relevant for toxin adsorption by the composite. Similar maximum ZEN adsorbed amounts under the applied experimental conditions (14.4 mg/g) at both pH values suggested that its adsorption was independent of the pH. This study reported for the first time that a novel composite of B with ChM and HB showed promising antimicrobial and antioxidant properties and was an efficient adsorbent for mycotoxin ZEN. Full article

Endophyte fungi (EF) are considered a new and valuable reservoir of bioactive molecules of biotechnological interest for pharmacy, agricultural and forestry industries. In this study, thirty EFs, isolated from three Chilean Nothofagus species (N. alpina, N. dombeyi, N. oblicua) were identified and cultured in submerged liquid fermentations aimed at searching for natural active substances. The extracts obtained were evaluated against pathogenic bacteria and fungi. Sixteen extracts (53.3%) presented antibacterial and fourteen (46.6%) presented antifungal activities in different intensities. Extracts from isolates Coryneum sp.-72 and P. cinnamomea-78 exhibited the highest antimicrobial activity. Using bioautography, the compounds responsible for the antimicrobial activity exhibited by Coryneum sp.-72 and P. cinnamomea-78 were detected and characterized. Coryneum sp.-72 showed bactericidal properties at 200 μg/mL and bacteriostatic effects at 50 μg/mL against B. cereus, B. subtilis, L. monocytogenes and S. aureus. MIC values indicated that P. cinnamomea-78 exhibited a strong fungistatic and fungicidal effect against B. cinerea and C. gloesporioides at 10–50 μg/mL. Isolates were grouped in the following order: Botryosphaeriales, Diaporthales, Eurotiales, Helotiales, Hypocreales, Pleosporales, Magnaporthales, Sordariales and Polyporales. EF isolated, identified and evaluated constitute the first report for Chilean Nothofagus genus. Full article

Infectious pathogens pose serious threats to public health, necessitating the development of more antimicrobials. In this study, oligohydroxybutyrates were obtained through the catalyzed polymerization of β-butyrolactone using N, N-dimethyl-4-aminopyridine (DMAP) and aluminum isopropoxide [Al(OiPr)₃] and applied as sustainable antimicrobial agents. The poly3-hydroxybutyrate (PHB) oligomers exhibited broad-spectrum antibacterial activities against both Gram-negative (E. coli) and Gram-positive (S. aureus) model bacteria. Additionally, PHB oligomers displayed robust (inhibiting rate: >95%) and rapid (action time: <20 min) antiviral activity against three notorious single-stranded RNA viruses, that is, influenza A virus (H1N1 and H3N2) and coronavirus (SARS-CoV-2). In particular, a comprehensive set of advanced experimental characterizations, including FT-IR, ¹H- and ¹³C-NMR, and H-ESI-MS/MS, was applied to analyze their chemical structures. The results confirmed the loss of terminal hydroxyl groups in the PHB intermediate and end products associated with theoretical calculations. These findings will also help provide deep insight into the major chain growth mechanism during the synthesis of PHB. The structural variations, which were treated as unwanted side reactions, were identified as a pivotal factor by deactivating the terminal hydroxy during chain growth. Their effective sterilization properties and degradability endowed the as-prepared PHB oligomers with a promising biomedical potential, including for use as disinfectants, sanitizers, and antiseptics. Full article

Eugenia pyriformis Cambess., popularly known as uvaia, is a native Brazilian species belonging to the Myrtaceae family that has attracted pharmacological interest due to its richness in bioactive secondary metabolites. Previous studies have reported antimicrobial and antioxidant activities of the essential oil obtained from its leaves, reinforcing its therapeutic potential. In this context, the present study aimed to extract and characterize the essential oil from E. pyriformis leaves cultivated in the mountainous region of Rio de Janeiro, Brazil, and to evaluate its anti-inflammatory potential through in vitro and in vivo models. Gas chromatography mass spectrometry (GC–MS) analysis revealed a predominance of sesquiterpene hydrocarbons, mainly γ-muurolene, δ-cadinene, and β-caryophyllene. The oil exhibited significant anti-edematogenic activity in carrageenan-, prostaglandin E₂-, and bradykinin-induced paw edema models in adult female Swiss mice, suggesting modulation of inflammatory mediators, possibly through inhibition of the cyclooxygenase (COX) pathway. Conversely, no effect was observed in the compound 48/80-induced model, indicating the absence of activity on histamine- and serotonin-mediated processes. In vitro assays demonstrated that the oil reduced TNF-α and IL-1β gene expression in RAW 264.7 macrophages, confirming its ability to modulate pro-inflammatory cytokines. Taken together, these findings demonstrate that the essential oil of E. pyriformis exerts anti-inflammatory activity through multiple targets. Full article

Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in Sarawak, Malaysian Borneo, where it is represented by a unique gentamicin-susceptible population. Despite trimethoprim-sulfamethoxazole (co-trimoxazole) being the cornerstone of eradication therapy, emerging reports of elevated minimum inhibitory concentrations (MICs) among Sarawak isolates have raised concerns over its clinical efficacy. We performed a retrospective and comprehensive antibiotic susceptibility assessment of clinical B. pseudomallei isolates from hospitals across Sarawak. Susceptibility to trimethoprim-sulfamethoxazole was determined using disk diffusion and the E-test, interpreted by both CLSI and EUCAST guidelines. Resistance to the individual components, trimethoprim and sulfamethoxazole, was characterized by broth microdilution. The results demonstrated a high prevalence of trimethoprim-sulfamethoxazole susceptibility, with 96.3% of isolates susceptible by CLSI criteria and 97.6% by EUCAST criteria. Interestingly, broth microdilution revealed that resistance to trimethoprim and sulfamethoxazole individually did not confer resistance to the synergistic combination. Our analysis validated CLSI guidelines as the most reliable standard for antimicrobial resistance surveillance in this region. This study provides evidence that trimethoprim-sulfamethoxazole remains effective for melioidosis treatment in Sarawak, offering crucial reassurance to clinicians. The paradoxical finding of susceptibility to the drug combination despite resistance to its individual components underscores the critical importance of the synergistic activity of trimethoprim-sulfamethoxazole and highlights the need for further investigation into the molecular basis of resistance in this distinct B. pseudomallei population. Full article

Background/Objectives. Lactiplantibacillus plantarum CRL681 has previously demonstrated a strong antagonistic effect against Escherichia coli O157:H7 in food matrices; however, the molecular mechanisms underlying this activity remain poorly understood. Since initial interactions between beneficial bacteria and pathogens occur mainly at the cell surface and in the extracellular environment, the characterization of the bacterial secretome is essential for elucidating these mechanisms. In this study, the secretome of L. plantarum CRL681 was comprehensively characterized using an integrated in silico and in vitro approach. Methods. The exoproteome and surfaceome were analyzed by LC-MS/MS under pure culture conditions and during co-culture with E. coli O157:H7. Identified proteins were functionally annotated, classified according to subcellular localization and secretion pathways, and evaluated through protein–protein interaction network analysis. Results. A total of 275 proteins were proposed as components of the CRL681 secretome, including proteins involved in cell surface remodeling, metabolism and nutrient transport, stress response, adhesion, and genetic information processing. Co-culture with EHEC induced significant changes in the expression of proteins associated with energy metabolism, transport systems, and redox homeostasis, indicating a metabolic and physiological adaptation of L. plantarum CRL681 under competitive conditions. Notably, several peptidoglycan hydrolases, ribosomal proteins with reported antimicrobial activity, and moonlighting proteins related to adhesion were identified. Conclusions. Overall, these findings suggest that the antagonistic activity of L. plantarum CRL681 against E. coli O157:H7 would be mediated by synergistic mechanisms involving metabolic adaptation, stress resistance, surface adhesion, and the production of non-bacteriocin antimicrobial proteins, supporting its potential application as a bioprotective and functional probiotic strain. Full article

The misuse of antibacterial agents has contributed to the growing prevalence of antibiotic resistance, highlighting an urgent need to explore alternative anti-infection therapeutic strategies. Antimicrobial peptides (AMPs) are naturally occurring molecules. They exhibit broad-spectrum antimicrobial activity and represent promising candidates for the development of novel therapeutics. A cysteine-rich antimicrobial peptide was identified and characterized from the genome of Tigriopus japonicus and designated “TjRcys1”. The precursor form of TjRcys1 comprises 96 amino acids. Structural analyses of TjRcys1 revealed random coils, two α-helices, and two β-strands. Recombinant TjRcys1 had inhibitory effects upon Staphylococcus aureus and Bacillus sp. T2, with a minimum inhibitory concentration of 64 μM for both. TjRcys1 did not show complete inhibition against Vibrio alginolyticus, Klebsiella pneumoniae, or Aeromonas hydrophila at 64 μM, but it did slow their growth rate. TjRcys1 could disrupt the permeability of the cell membrane of S. aureus. Transcriptomic analyses indicated that TjRcys1 could interfere with the ribosome biosynthesis and nucleotide metabolism of K. pneumoniae. Our results provide a valuable reference for the development of new AMPs and optimization of their design. Full article

Piscine lactococcosis is an emerging bacterial disease that threatens freshwater and marine aquaculture in the Mediterranean region. This study characterized isolates of Lactococcus garvieae and Lactococcus petauri from farmed fish through molecular identification, genomic typing and antimicrobial susceptibility testing. A total of 39 bacterial strains were analyzed using species-specific real-time PCR assays, multilocus sequence typing and broth microdilution to determine minimum inhibitory concentrations. Results suggest a temporal shift in freshwater systems, where L. garvieae predominated in earlier isolates (mainly ST13, CC4), while L. petauri (ST14, CC14) appears as the dominant species in recent years. In marine fish, only L. garvieae was detected, mainly ST95 (CC95), a lineage previously reported in Europe. Molecular variability was found in both species with lineages capable of infecting livestock and humans. Amoxicillin displayed promising results; florfenicol showed moderate activity, while flumequine exhibited no inhibitory effect. Oxytetracycline and trimethoprim–sulfamethoxazole showed variable results requiring prudent use. These region-specific susceptibility profiles provide updated baseline data to guide empirical antimicrobial therapy while awaiting laboratory confirmation, highlighting the evolution of lactococcosis in aquaculture and emphasizing the need for molecular surveillance, antimicrobial stewardship, and vaccine updates within a One Health framework to mitigate impacts on Mediterranean aquaculture and public health. Full article