Search Results (4,097)

Antimicrobial resistance represents a major global health challenge, highlighting the urgent need for alternative bioactive compounds from natural sources. This study investigated the phytochemical composition and antimicrobial potential of saponin-enriched extracts from the trunk bark of Argania spinosa (L.) Skeels, collected from two contrasting Algerian regions: the coastal area of Stidia (ES) and the Saharan region of Tindouf (ET). Extraction yields were comparable (approximately 12.6%). UHPLC-MS analysis revealed distinct phytochemical profiles, with ES enriched in oleanane-type saponins and flavonoids, whereas ET showed a higher abundance of bayogenin-type derivatives. Key compounds included arganine C, E, and J, as well as catechin and quercetin. Antimicrobial activity was evaluated using agar well diffusion and broth microdilution assays against clinically relevant microorganisms, including the reference strains Staphylococcus aureus and Listeria innocua, together with Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Proteus mirabilis, and Candida albicans. Both extracts exhibited broad-spectrum antimicrobial activity, although ES consistently showed lower Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal, Fungicidal Concentration (MBC)/(MFC) values than ET. MIC values ranged from 25 to 50 mg/mL for ES and from 50 to 100 mg/mL for ET. Synergistic interactions were observed between ES and gentamicin against S. aureus and between both extracts and kanamycin against K. pneumoniae. Membrane permeability assays demonstrated that both extracts increased bacterial membrane permeability, with ET producing a stronger permeabilizing effect. Atomic force microscopy of ES-treated cells revealed marked alterations in bacterial surface morphology, while molecular docking supported strong interactions of mi-saponin B and arganine derivatives with key bacterial targets. Collectively, these findings highlight the potential of A. spinosa bark saponins as natural antimicrobial agents and promising antibiotic adjuvants against multidrug-resistant pathogens. Full article

The increasing prevalence of antimicrobial resistance (AMR) has promoted the development of advanced biomaterials capable of overcoming the limitations of conventional antibiotics. In this context, metal nanoparticle hybrid hydrogels (MNHHs) have emerged as multifunctional platforms that integrate the high water-retention capacity and biocompatibility of hydrogels with the antimicrobial properties of metallic nanoparticles (MNPs). This review critically analyzes recent advances in the design, physicochemical properties, antimicrobial mechanisms, and biomedical applications of these systems. Current evidence demonstrates that MNHHs can achieve antimicrobial efficiencies above 98–99%, with minimum inhibitory concentrations as low as 0.78 µg mL⁻¹ and inhibition zones of up to 25 mm against clinically relevant pathogens. Furthermore, the incorporation of MNPs significantly improves the mechanical properties of hydrogels and enables controlled and sustained metal ion release for periods of up to 14 days. Despite these promising results, important challenges remain regarding cytotoxicity, release control, the lack of experimental standardization, and the limited understanding of long-term biological effects. Overall, MNHHs represent a promising strategy for infection control, regenerative medicine, and controlled drug delivery; however, their clinical translation still requires the development of reproducible, safe, scalable, and highly biocompatible systems. Full article

Co-contamination of biphenyl and heavy metals is widespread in industrial environments, but systematic studies on the simultaneous treatment of both pollutants using a single microbial strategy remain limited. In this study, we characterized the biphenyl degradation performance, metabolic pathway, transcriptomic response, and Cr(VI) tolerance of Rhodococcus sp. TG-1, and developed an alkali-modified biochar immobilization system to enhance its degradation efficiency for biphenyl under Cr(VI) stress. Degradation experiments were carried out under optimal conditions (30 °C, pH 7.0), and it was found that strain TG-1 degraded 76.84% of 300 mg/L biphenyl within 3 days. Intermediate metabolites were identified by LC-MS, and five key intermediates were detected, confirming that TG-1 metabolizes biphenyl via the classical 2,3-dihydroxybiphenyl dioxygenase pathway, with subsequent entry into the tricarboxylic acid cycle. Transcriptomic analysis was performed to profile gene expression, revealing 845 differentially expressed genes under biphenyl stress, including 672 upregulated genes significantly enriched in aromatic degradation pathways. Seven complete bph gene clusters responsible for biphenyl catabolism were also identified. Strain TG-1 exhibited high tolerance to Cr(VI), with a minimum inhibitory concentration (MIC) of 500 mg/L. However, its biphenyl degradation efficiency dropped to 51.32% in the presence of 200 mg/L Cr(VI). After immobilization using alkali-modified straw biochar (JBC), heavy metal toxicity was alleviated, and the biphenyl removal rate increased to 99.30% under co-contamination conditions. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) analyses confirmed that TG-1 was stably loaded onto the biochar surface through hydrogen bonding and electrostatic interactions. Altogether, this study provides a promising bacterial strain and a green immobilization strategy for enhancing biphenyl removal in the presence of Cr(VI), offering a practical approach for the treatment of environments co-contaminated with aromatic compounds and heavy metals. Full article

Staphylococcus aureus is a leading cause of bacterial keratitis and antimicrobial resistance-associated death globally. This study aimed to evaluate the efficacy of CaD23, a human-derived hybrid antimicrobial peptide (AMP), in combination with antibiotics in treating S. aureus infections. The efficacy of CaD23 and six medically important antibiotics (amikacin, cefuroxime, chloramphenicol, fosfomycin, vancomycin and levofloxacin) was examined against six strains of methicillin-sensitive and methicillin-resistant S. aureus using a minimum inhibitory concentration (MIC) assay. CaD23–antibiotic interactions were evaluated using checkerboard and time–kill kinetics assays. 3,3′-dipropylthiadicarbocyanine iodide (DiSC_3,5) cytoplasmic membrane depolarisation assay was performed to examine the mechanism of action. Overall, CaD23 exhibited good efficacy against all MSSA and MRSA (MIC = 16–32 μg/mL [6.7–13.3 μM]). Of 20 peptide–antibiotic–organism combinations, 19 (95%) combinations demonstrated positive interactions, with six (31.6%) and 13 (68.4%) exhibiting synergistic (FICI = 0.293–0.412) and additive effects (FICI = 0.521–0.890), respectively. CaD23 was able to achieve complete bacterial eradication significantly faster than cefuroxime and levofloxacin (15 min vs. 8–24 h). When used at a sub-MIC concentration, CaD23 could accelerate the killing of S. aureus of cefuroxime from 8–24 h to within 1 h and enhance the activity of levofloxacin by 90%. CaD23 was shown to rapidly depolarise the inner membrane of S. aureus within seconds of the treatment. In conclusion, CaD23–antibiotic combination therapy serves as a useful strategy for tackling drug-resistant ocular and systemic S. aureus infections. Full article

Tropical coastal waters are increasingly recognized as critical reservoirs for virulent, antibiotic-resistant enteric pathogens, yet seasonal dynamics governing their spatial distribution remain poorly characterized. We hypothesized that hydrological shifts and anthropogenic nutrient enrichment drive the seasonal distribution, virulence profiles, and antimicrobial resistance (AMR) of Escherichia coli, Salmonella spp., and Shigella spp. in the Jaffna Peninsula, Sri Lanka. Across 25 coastal sites during dry and transitional seasons, we integrated physicochemical water quality assessment, culture-based enumeration, PCR-based virulence gene profiling, Minimum Inhibitory Concentration (MIC) assays, GIS mapping, and statistical analyses. Key water quality parameters, including ammonium, nitrite, and total phosphorus, showed significant seasonal variation (p < 0.05), reflecting distinct hydrological regimes across seasons. A total of 220 E. coli, 200 Salmonella spp., and 100 Shigella spp. isolates were examined for virulence gene profiles and antibiotic tolerance. E. coli was detected at 80–88% of sites, Salmonella spp. at 72–88%, and Shigella spp. at 32–48%. Among E. coli isolates, stx1 was detected at 20–28% of sites and eae at 16% across both seasons. The stn gene was detected in Salmonella spp. at 12–28% of sites seasonally. Virulence profiling confirmed STEC harbouring stx1, stx2, and eae; Salmonella spp. carried stn; and Shigella spp. possessed invasion-associated genes. Trimethoprim–sulfamethoxazole resistance was recorded in 63.2% of E. coli, 33.0% of Salmonella spp., and 31.0% of Shigella spp. isolates at the lowest tested concentration of 4 µg/mL., while ciprofloxacin and piperacillin–tazobactam retained greater efficacy. Correlation analyses revealed significant associations among faecal contamination, nutrient enrichment, and virulence gene prevalence, implicating untreated sewage discharge and eutrophication as likely ecological factors associated with pathogen occurrence. These findings designate the Jaffna coastal zone as a significant reservoir of virulent AMR enteric pathogens, underscoring the urgent need for integrated One Health surveillance and seasonally adaptive coastal water quality management. Full article

Candida auris is a multidrug-resistant fungal pathogen associated with high mortality in healthcare settings. Although colonization is recognized as the harbinger of invasive infection, predicting which patients will develop bloodstream infection (BSI) and when this transition will occur remains a clinical challenge. In this study, patients aged ≥18 years with C. auris colonization identified at İzmir City Hospital between January 2023 and June 2025 were retrospectively analyzed. Colonization was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Of 71 colonized patients (median age 65 years; 69.0% male; 93.0% intensive care unit (ICU)-admitted), 31 (43.7%) developed bloodstream infection (BSI). In-hospital mortality was 62.0%, rising to 74.2% in the BSI group, though this difference did not reach statistical significance (p = 0.105). Competing risks analysis using the Aalen–Johansen method showed a cumulative BSI incidence of 38.2% (95% confidence interval (CI): 28–50%) by day 10 and 43.0% (95% CI: 32–54%) by day 30 following colonization detection. On multivariate logistic regression, diabetes mellitus was the sole variable independently associated with a lower risk of BSI development (adjusted odds ratio (OR): 0.19; 95% CI: 0.06–0.68; p = 0.010); this finding was directionally consistent but did not reach statistical significance in the multivariable Fine–Gray competing risks model (subdistribution hazard ratio (SHR): 0.334; 95% CI: 0.108–1.040; p = 0.057). All 40 tested isolates had high fluconazole minimum inhibitory concentration (MIC) values; micafungin susceptibility was 92.5%, while anidulafungin resistance was observed in 32.5% of isolates. Our findings demonstrate that nearly half of colonized patients developed BSI, with no identifiable safe window for intervention, underscoring the necessity of sustained infection control measures and susceptibility-guided antifungal therapy. Full article

Excessive application of chemical preservatives has raised increasing concerns regarding food safety and human health, prompting the search for safer natural alternatives. Lavender essential oil (LEO), a plant-derived antimicrobial agent, has been considered a promising substitute for synthetic preservatives, but its high volatility and poor water solubility limit its practical application. In this study, LEO nanoemulsions were fabricated via high-pressure homogenization using sodium caseinate (SC) and tea polyphenols (TPs) as composite emulsifiers. The preparation process was optimized using a three-factor, three-level orthogonal design, and the physicochemical properties, storage stability, and antibacterial activity were systematically investigated. The optimal preparation conditions were determined as an SC/TP mass ratio of 2:1, homogenization pressure of 70 MPa, and 7 homogenization cycles. The optimized nanoemulsion exhibited a droplet size of 130–210 nm, zeta potential of −30.89 mV, and encapsulation efficiency of 98.61%, with typical shear-thinning behavior and excellent storage stability. The percentage of free LEO remained below 7.5% within 15 days, indicating high stability, and the release behavior followed a zero-order kinetic model. The prepared nanoemulsion showed significant antibacterial activity against Staphylococcus aureus and Escherichia coli, with a minimum inhibitory concentration (MIC) of 62.5 μg/mL for both strains. This study confirms that the SC/TP composite interface can effectively stabilize LEO nanoemulsions, providing a theoretical basis for the development of natural and efficient food preservatives. Full article

Ocimum species (family Lamiaceae) are among the most extensively utilized medicinal plants across low- and middle-income countries (LMICs), yet their pharmacological evidence base has not been comprehensively synthesized within an LMIC healthcare framework. A systematic review was conducted following PRISMA 2020 guidelines and a prospectively registered protocol (PROSPERO). Five electronic databases, PubMed, Scopus, Embase, Web of Science, and Google Scholar, were searched from January 2010 to December 2025. Studies reporting ethnobotanical, phytochemical, or pharmacological data on any Ocimum species were eligible. The study selection, quality assessment and data extraction were done by two independent reviewers utilizing Rayyan software. Findings were synthesized using a narrative approach. Ninety-seven studies were included. O. basilicum, O. tenuiflorum, and O. gratissimum were most studied. Key bioactive constituents rosmarinic acid, eugenol, linalool, β-caryophyllene, and ursolic acid, demonstrated consistent antimicrobial [minimum inhibitory concentration (MIC): 0.31–1.25 mg/mL], antioxidant [2,2-diphenyl-1-picrylhydrazyl (DPPH) IC₅₀: 12.5–89.3 µg/mL], anti-inflammatory (35–55% edema reduction), and antidiabetic (α-glucosidase IC₅₀: 0.3–1.5 mg/mL) activities. Larvicidal efficacy exceeding 90% against Anopheles spp. was demonstrated in field trials. The safety profile was broadly favorable (LD₅₀ > 5000 mg/kg). Ocimum species represent a pharmacologically credible and preclinically well-supported botanical resource with practical relevance for LMIC health systems, particularly in antimicrobial, antidiabetic, anti-inflammatory, and vector-control applications. To realize their therapeutic potential, future research must prioritize LMIC-contextualized randomized controlled trials, standardized phytochemical reporting, and chemotype-aware product development. Full article

Allium sativum is widely consumed and studied plant for its potential health-promoting effects. Despite its widespread use, the impact of different extraction methods on the biological efficacy and specific phytochemical composition of garlic has not yet been fully elucidated. This study investigated the phytochemical profile, antibacterial, antioxidant, and anti-inflammatory properties of ethanolic and aqueous extracts of Moroccan-grown A. sativum using in vitro assays and in silico analyses. Total phenolic and flavonoid contents were determined by colorimetric methods, while phenolic aglycones were identified by HPLC. Antibacterial activity was evaluated by disc diffusion and determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, antioxidant capacity by DPPH, TAC, and FRAP assays, and anti-inflammatory activity through protein denaturation inhibition. ADMET profiling was performed to predict pharmacokinetic and toxicological properties of the identified compounds. The ethanolic extract exhibited higher flavonoid and phenolic contents, reaching 13.27 ± 0.01 mg quercetin/_gextract and 1.57 ± 0.02 mg GAE/_gextract, respectively. HPLC analysis identified syringic, caffeic, ferulic, p-coumaric, and chlorogenic acids, as well as kaempferol and quercetin, whereas apigenin was detected only in the ethanolic extract under the present extraction and analytical conditions. Both extracts inhibited MRSA and E. coli but showed no activity against Pseudomonas aeruginosa. Docking analyses suggested favorable interactions between the identified compounds and bacterial target proteins. The ethanolic extract displayed stronger antioxidant activity, with DPPH IC₅₀ and TAC EC₅₀ values of 1.134 and 2.527 mg/mL, respectively. No ferric reducing activity was detected under the tested conditions. Protein denaturation inhibition ranged from 30.68% to 90.37%, with the aqueous extract showing significantly greater activity (p < 0.003). Overall, extraction-dependent differences in phenolic composition appear to influence the biological properties of A. sativum extracts, warranting further mechanistic and in vivo investigations. Full article

Colorectal cancer (CRC) has been increasingly associated with gut microbiota dysbiosis and the presence of specific bacterial pathogens. This study evaluated the in vitro growth-inhibitory activity of 18 biologically active compounds, including phytochemicals, synthetic analogs, and clinically used antibiotics, against CRC-associated bacterial strains. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method and analyzed in relation to chemical structure. Conventional antibiotics, particularly tetracycline and ciprofloxacin, exhibited the strongest antibacterial activity. Among non-antibiotic compounds, nitroxoline and carbadox showed moderate activity, whereas quaternary benzylisoquinoline-derived alkaloids and polyphenols were less effective. Structure–activity relationship analysis suggested that aromatic heterocyclic scaffolds, electron-withdrawing substituents, and metal-chelating groups contribute to antibacterial potency. We obtained novel MIC data for several compounds, including ferron and oxyquinoline, against underexplored CRC-associated bacterial strains. These findings expand current knowledge of the antibacterial activity of structurally diverse compounds against CRC-associated bacteria and provide a basis for future studies on microbiota-targeted antimicrobial strategies. Full article

Acanthamoeba keratitis (AK) and mycotic keratitis (MK) are severe infectious diseases of the cornea. A major challenge to treatment is the poor bioavailability of conventional eye drop formulations, resulting in significant loss of the therapeutic compound. The present study describes the preparation of self-nanoemulsifying drug delivery systems (SNEDDSs) utilizing 3D-molded inserts as a vehicle for the co-delivery of voriconazole (VOR) and diclofenac sodium (DIC). Characterization of the SNEDDS and the 3D-molded inserts involved analysis of droplet size, polydispersity index (PDI), and zeta potential (ZP), followed by an ex vivo transcorneal permeation. Careful optimization of the SNEDDS composition was fundamental for obtaining a nanoemulsion with a droplet size under 100 nm, a PDI below 0.35, and a variable ZP (ranging from −14.6 ± 0.1 to 16.3 ± 2.4 mV). These properties facilitated a marked improvement in voriconazole’s solubility and subsequent transcorneal permeability. The investigation of the inserts revealed that the in vitro drug release could be tailored for immediate release or extended release. Moreover, ex vivo permeation studies demonstrated that the inserts delivered voriconazole to the cornea at concentrations more than the minimum inhibitory concentration. This work successfully demonstrates the formulation of a patient-centric, personalized drug delivery platform for the treatment of AK and MK. Full article

Invasive candidiasis caused by drug-resistant Candida species represents a critical global health challenge, with few novel therapeutic scaffolds under development. Here, silver nanoparticles were synthesized using a 21-day fermented Chun Mee kombucha tea extract (K-AgNPs) and characterized by UV-Vis spectroscopy, transmission electron microscopy, nanoparticle tracking analysis, and Fourier-transform infrared spectroscopy. LC-MS/MS profiling of the kombucha substrate documented a phytochemical landscape dominated by epigallocatechin (up to 122,631 µg/mL) and epigallocatechin gallate (up to 415 µg/mL), with a progressive ~80% decline in epicatechin and concomitant increases in gallic acid and chlorogenic acid across the 21-day fermentation. K-AgNPs obtained were spherical, 19.4 nm (±7.9 nm SD) in diameter, with a surface plasmon resonance peak at 415 nm. FTIR confirmed phenolic, carboxylate, and glycosidic surface capping. Antifungal susceptibility testing against eight Candida species, including the WHO critical–priority pathogen Candidozyma auris, showed concordant minimum inhibitory and minimum fungicidal concentrations of 0.80–1.60 µg/mL, confirming fungicidal activity. In vivo evaluation in Galleria mellonella larvae across six infection models demonstrated that K-AgNP treatment at the species-specific MIC significantly improved larval survival versus untreated infected controls (p < 0.01–0.001), while nanoparticle-only groups maintained ≥98% survival, indicating negligible toxicity. Co-treatment amplified total hemocyte mobilization, and K-AgNP-only larvae maintained hemocyte viability above 96% at all time points, indistinguishable from negative controls. Together, these findings demonstrate antifungal activity of K-AgNPs across the genus Candida in standardized in vitro and in vivo settings and provide justification for further investigation, including head-to-head comparison against licensed antifungals and physicochemical validation of nanoparticle stability under assay conditions. Full article

Background/Objectives: Neisseria gonorrhoeae is a high-priority pathogen for the development of new therapeutic alternatives. Efflux pumps are attractive drug targets because their inactivation influences N. gonorrhoeae susceptibility to multiple antimicrobials. Since most gonococcal efflux systems are energy-dependent, interference with energy metabolism and membrane transport may indirectly compromise efflux activity. Efflux inhibitors may increase intracellular antibiotic concentration, although this requires validation in resistant strains. The most effective efflux inhibitors interfere with energy metabolism, affecting several physiological processes, including efflux. In this work, we used an in silico drug repurposing strategy targeting proteins involved in membrane transport and energy metabolism in N. gonorrhoeae. A subset of candidate drugs were subsequently evaluated in vitro using only the reference strain N. gonorrhoeae ATCC 49226. Methods: Predicted drug–target interactions were identified using publicly available databases such as DrugBank and STITCH. Minimum inhibitory concentrations (MICs) of selected drugs against N. gonorrhoeae were determined by microdilution. Changes in intracellular ethidium bromide accumulation were assessed by real-time fluorometry as an indirect indicator of possible efflux-related interference. Results: In silico analysis identified 32 predicted targets associated with 57 approved drugs. Triclabendazole and dequalinium showed the lowest MIC values of the tested compounds (2 and 4 mg/L, respectively). Ketotifen and verapamil demonstrated activity consistent with possible efflux interference, as indicated by increased ethidium bromide accumulation. Atovaquone showed adjuvant-like effects in combination assays, suggesting that mechanisms other than efflux-related interference may contribute to its activity. Conclusions: Overall, this preliminary study identifies approved drugs with antimicrobial or adjuvant activity against a single N. gonorrhoeae reference strain, supporting further investigation in clinically relevant and efflux-variant strains. Full article

The dimorphic fungus Talaromyces marneffei causes talaromycosis, a life-threatening fungal disease with limited treatment options. Olorofim, a first-in-class orotomide antifungal that targets pyrimidine synthesis essential for fungal growth, has low minimum inhibitory concentration (MIC) against T. marneffei and clinical efficacy against other invasive fungal diseases. Here, we tested the hypothesis that olorofim synergistically enhances amphotericin B (AmB), a potent membrane-targeting antifungal, against T. marneffei in 55 clinical isolates using a validated colorimetric checkerboard assay. The MIC was defined as the lowest drug concentration inhibiting ≥ 95% of fungal growth. Drug interactions were assessed using the fractional inhibitory concentration index (FICI), which defines ≤0.5 as synergy, 0.5 < FICI ≤ 4.0 as indifference, and FICI > 4 as antagonism. We found that interactions between AmB and olorofim were indifferent across all 55 isolates (0.5 < FICI ≤ 1.03). Time-kill assays showed an expected concentration-dependent fungicidal activity for AmB, but a concentration-independent fungistatic activity for olorofim against T. marneffei. Combinations of AmB and olorofim were also indifferent in time-kill experiments. Although synergy was not observed, and olorofim is unlikely to enhance AmB induction therapy, olorofim may have a role in the consolidation and maintenance therapy of talaromycosis. Full article

The genus Capsicum is widely used worldwide for its culinary value and functional potential. The objective of this study was to evaluate the bioactive compounds, antioxidant and antimicrobial activity of sweet and hot pepper at different stages of ripeness. Six varieties of peppers at five stages of ripeness were analysed. Mineral parameters (Ca, Fe, Na, K, Mg) were determined by atomic absorption spectrophotometry, while bioactive compounds (vitamin C, organic acids, carotenoids, and phenols) were analysed by liquid chromatography. Antioxidant activity was evaluated using ABTS and DPPH assays, and antimicrobial activity was assessed by minimum inhibitory concentration against bacteria and yeasts. Multivariate analyses (PCA and heatmap) were carried out at a significance level of p < 0.05. The results showed that genotype was the main determinant of variability, surpassing the effect of ripeness. Potassium was the predominant mineral (3431.5 mg/100 g DW) in Malagueta chilli M5. Variety-specific peaks were identified, notably vitamin C in Habanero chilli (M3) (10,319.5 mg/100 g DW), capsaicin in Malagueta chilli (M5) (1949.8 mg/100 g DW), and carotenoids in Orange medium peppers (M5) (9495.8 mg/100 g DW). Antioxidant activity was higher in hot varieties (41.3 mmol ET/100 g DW in Habanero chilli (M2) by DPPH), while antimicrobial activity varied against Escherichia coli (2.6 mg/mL in Yellow medium peppers (M4)), Staphylococcus aureus (5.2 mg/mL in Orange medium pepper), and Streptococcus mutans (2.0 mg/mL in Jalapeño chilli), with low MIC values. Multivariate analyses confirmed that chemical and biological variability is primarily structured by genotype. Full article