Search Results (3,461)

This study examined Kefiran, an exopolysaccharide derived from milk kefir grains, as a novel biopolymer for encapsulating phenolic extracts from sunflower cake and its antimicrobial properties in the development of natural and functional food ingredients. Kefiran was obtained from kefir grains using three extraction protocols: hot water (M1), hot water with 30% trichloroacetic acid (M2), and mild heat combined with ultrasound at 60 °C (M3). The ultrasound-assisted method produced the highest carbohydrate concentration. Spectrophotometric assays (phenol–sulfuric and Bradford), Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and water-holding capacity were employed to characterize the composition, structure, and morphology of the extracts, revealing well-preserved polysaccharide fingerprints and a highly porous microstructure, consistent with their potential application in food systems. Kefiran was then evaluated as an encapsulating agent in complex coacervation at pH 3.75, using three Kefiran-based wall formulations (M1, M2, and M3) with gum arabic and whey protein isolate (WPI) as co-wall materials, and their performance was compared with gum arabic and WPI controls. Across formulations, coacervate microcapsules achieved high encapsulation efficiencies (83–93%), tunable particle sizes, and predominantly negative zeta potentials, indicative of good colloidal stability. The Kefiran extract and coacervate microcapsules demonstrated significant antioxidant and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans, with minimum inhibitory concentrations ranging from 250 to 1000 µg/mL. The findings support ultrasound-extracted Kefiran as a multifunctional biopolymer suitable for bioactive delivery and as a natural antimicrobial component in advanced functional food formulations. Full article

Azole resistance in Candida albicans is an increasing clinical challenge. Upc2 is a key transcription factor regulating ergosterol biosynthesis, but its additional roles in azole tolerance remain unclear. This study investigated whether Upc2 contributes to azole resistance through pathways beyond ergosterol synthesis. Chemical sensitivity screening, RNA sequencing, flow cytometry, and molecular assays were performed to compare wild-type C. albicans and the upc2Δ/upc2Δ mutant under fluconazole (FLC) treatment. The UPC2 gene deletion affected physiological processes that are dependent on the calcineurin signaling pathway and led to an overall negative enrichment trend in the unfolded protein response (UPR) pathway gene set. Mechanistically, the UPC2 gene deletion impaired unconventional splicing of HAC1 mRNA, leading to accumulation of unfolded proteins and phenotypically its deletion enhanced sensitivity of C. albicans to FLC in planktonic growth, hyphal development, and biofilm formation. Our findings reveal that Upc2 regulates proteostasis in C. albicans, and its absence enhances FLC efficacy by disrupting the UPR pathway. Targeting Upc2-mediated UPR signaling may represent a promising strategy to combat azole resistance. Full article

The efficacy of plant-derived antimicrobials in meat systems is frequently limited by interactions with proteins, lipids, and other food matrix components that reduce the bioavailability and antimicrobial activity of phytochemicals. This study evaluated the antimicrobial effectiveness of Verbascum sinaiticum (V. sinaiticum) leaf extract encapsulated using maltodextrin (MD), gum arabic (GA), and a maltodextrin–gum arabic blend (MDGA, 8:2 w/w) through freeze-drying for application in raw beef during refrigerated storage (4 °C). The encapsulation systems exhibited process yields of 42.5–54.7%, encapsulation efficiencies of 78.3–92.5%, and loading capacities of 18.5–24.3 mg GAE/g DW, with MDGA showing the highest encapsulation efficiency. The effects of encapsulation on microbial inhibition, physicochemical properties, and sensory quality were investigated over 15 days of storage. Aerobic plate counts in the control increased from 3.04 to 8.26 log CFU/g, whereas encapsulated treatments showed significantly lower final counts (p < 0.05), reaching 7.89 log CFU/g (MD), 7.96 log CFU/g (MDGA), and 7.95 log CFU/g (GA). Similarly, encapsulated treatments reduced Escherichia coli counts during storage, with maltodextrin (MD) exhibiting the greatest inhibitory effect (6.23 × 10⁵ CFU/g) compared with the control (6.93 × 10⁵ CFU/g) on day 15. However, reductions in Staphylococcus aureus, E. coli, Candida albicans, and Bacillus cereus remained below 1 log CFU/g, indicating limited antimicrobial efficacy under the tested conditions. All encapsulated treatments slowed pH increases during storage (6.20–6.34) relative to the control (6.62) on day 15 and preserved aroma quality throughout the storage period. Overall, encapsulation improved the antimicrobial performance of V. sinaiticum extract compared with the free extract, particularly in MD-based systems; however, the antimicrobial effects in beef remained modest. These findings highlight both the potential and current limitations of encapsulated plant-derived antimicrobials for meat preservation and emphasize the need for optimized delivery systems to enhance efficacy in complex food matrices. Full article

This study aimed to compare the chemical composition and antimicrobial activity of essential oils obtained from the rhizomes and leaves of Conamomum pierreanum (Zingiberaceae), and to evaluate interactions of selected constituents with microbial targets using molecular docking and molecular dynamics simulations. Gas chromatography–mass spectrometry (GC-MS) identified 21 compounds in the rhizome essential oil (EO) and 10 in the leaf EO of C. pierreanum, with 1,8-cineole (54.44% and 75.73%, respectively) as the predominant constituent. Notably, the rhizome EO was uniquely characterized by epi-γ-eudesmol (3.47%) and isobornyl acetate (3.39%), which were absent in the leaf oil. In vitro assays revealed that the rhizome EO possessed stronger antibacterial and antifungal activities (MIC = MBC = MFC = 0.4%) compared to the leaf EO (0.8%) against Staphylococcus aureus and Candida albicans. Molecular docking identified epi-γ-eudesmol as the most potential ligand, exhibiting remarkably high binding affinities for S. aureus DHFR (−8.1 kcal/mol) and C. albicans CYP51 (−8.5 kcal/mol), significantly outperforming the major constituents. A total of 100 ns molecular dynamics simulations and MM-PBSA analysis further confirmed the structural stability and energetically favorable binding of these complexes, with epi-γ-eudesmol maintaining a low average RMSD (<1.2 Å) throughout the simulation. The enhanced efficacy of the rhizome oil is attributed to the synergistic contribution of these high-affinity minor constituents. These findings suggest that C. pierreanum rhizome EO may serve as a potential source of bioactive compounds for antimicrobial applications, warranting further investigation. Full article

Candidemia is a major healthcare-associated bloodstream infection with high mortality, requiring ongoing surveillance to guide management. This retrospective study analyzed 306 candidemia episodes diagnosed between 2015 and 2024 at a Spanish tertiary-care hospital, comparing two periods (2015–2019 vs. 2020–2024). The overall incidence was 0.79 episodes per 1.000 admissions, with peaks in 2021 and 2024. Candida albicans was the most common species (44.8%), followed by Candida parapsilosis (19.0%) and Nakaseomyces glabrata (15.7%). A significant epidemiological shift occurred in the later period, with increased C. albicans, decreased C. parapsilosis, and emergence of N. glabrata as the second-most frequent species. ICU-related cases rose significantly during the COVID-19 period. Diagnostic turnaround times improved, including faster blood culture positivity and species identification by MALDI-TOF, supported by rapid PCR testing with high sensitivity (91.7%). Antifungal resistance to fluconazole was notable in N. glabrata (48.1%). Empirical echinocandin use increased, alongside greater targeted fluconazole therapy. Antimicrobial stewardship interventions, mainly de-escalation strategies, were widely implemented after 2019. Overall mortality was 40.8%, with a decline observed in 2023–2024. These findings suggest that integrated diagnostic and stewardship strategies may improve outcomes, though causal relationships require further study. Full article

Vulvovaginal candidiasis (VVC) is a common fungal infection among reproductive-age women and is increasingly challenged by the emergence of non-albicans Candida species and reduced azole susceptibility. This prospective cross-sectional study investigated 235 symptomatic reproductive-age women attending two healthcare facilities in Ho Chi Minh City, Vietnam, to determine VVC prevalence, Candida species distribution, pregnancy-associated patterns, antifungal susceptibility, and diagnostic performance. Vaginal swabs were cultured on Sabouraud Dextrose Agar and CHROMagar™ Candida, while species identification was confirmed by PCR-RFLP targeting the ITS region. Susceptibility to fluconazole and clotrimazole was assessed using the disk diffusion method. Candida spp. was detected in 55.7% of participants. C. albicans accounted for 50.3% of isolates, whereas non-albicans Candida species represented 49.7%, indicating a substantial species shift. VVC was more frequent among pregnant women, particularly in the third trimester. Most C. albicans, C. tropicalis, and C. parapsilosis isolates remained susceptible to azoles; however, C. glabrata showed markedly reduced susceptibility to fluconazole and clotrimazole. CHROMagar™ Candida reliably identified C. albicans but misclassified several non-albicans Candida isolates compared with PCR-RFLP. These findings highlight the need for routine species-level diagnosis, antifungal susceptibility testing, and strengthened VVC surveillance in reproductive and antenatal healthcare settings in Vietnam. Full article

Background: Fungal ocular infections, including keratitis and endophthalmitis, remain difficult to treat due to limited antifungal efficacy, poor tissue penetration, and biofilm-mediated resistance. This study evaluated the antifungal and host-protective potential of N-(4-methoxycinnamoyl)-anthranilic acid (NMCA) against Candida albicans and the multidrug-resistant Candidozyma auris. Methods: The antifungal activity of NMCA was assessed by analyzing fungal viability over time, ergosterol levels, and its interaction with fluconazole. Its antibiofilm activity was evaluated through biomass and metabolic activity measurements, together with the expression of genes involved in adhesion (ALS3, ALS5, HWP1) and membrane homeostasis (ERG11, OLE1). In addition, infected epithelial models were used to investigate epithelial damage, intracellular fungal burden, oxidative stress, and wound closure. Results: NMCA showed promising antifungal activity (MIC80 75 μg mL⁻¹ against C. albicans and 100 µg mL⁻¹ against C. auris), inducing a time-dependent reduction in fungal viability of about 4-log10 after 24 h. The compound also reduced ergosterol levels and showed synergistic interaction with fluconazole, as indicated by FICI values of 0.203 for C. albicans and 0.375 for C. auris. Moreover, NMCA markedly inhibited biofilm formation by reducing both biomass and metabolic activity up to approximately 80%, while modulating the expression of key adhesion- and membrane-related genes. Beyond its direct antifungal effects, NMCA reduced epithelial damage and intracellular fungal burden, attenuated oxidative stress, and significantly improved wound closure (reaching 76.26% and 90.46% closure in C. albicans- and C. auris-infected cells, respectively) in infected epithelial models. Conclusions: Although limited by the use of in vitro systems, these findings highlight the multifunctional profile of NMCA, which combines antifungal, antibiofilm, and tissue-protective activities. By simultaneously targeting pathogen viability, biofilm formation, and host cell integrity, NMCA appears to be a promising adjunctive candidate for the treatment of ocular fungal infections, where both pathogen eradication and tissue preservation are crucial for clinical outcomes. Full article

Rising triple-negative breast cancer (TNBC) cases and Candida infection risks during chemotherapy demand novel therapies, with metal-oxide nanocomposites emerging as a promising solution. In this study, we synthesized Ag-ZnO and Cu-ZnO nanocomposites as established quantitative links between their physicochemical properties, ion release behaviour, and biological activity, evaluating antifungal effects against Candida albicans (ATCC 90028) and Saccharomyces cerevisiae (ATCC 9763), and their anticancer potential against MDA-MB-231 cells (ATCC HTB-26). The results revealed Ag (~13–19 nm) and Cu (~4–8 nm) nanoparticles dispersed in a ZnO matrix, with XPS confirming mixed Ag⁰/Ag(I)/Ag(III) and Cu(I)/Cu(II) speciation. Ag-ZnO NC exhibited strong antifungal activity (MIC = 25 mg L⁻¹) against both fungi, while Cu-ZnO NC was only effective (MIC = 100 mg L⁻¹) against S. cerevisiae. Aqueous release of Ag⁺ was ~2.6-fold higher than Cu²⁺. Ag-ZnO NC induced marked ROS generation (~6-fold higher than S. cerevisiae) and dehydrogenase inhibition (6.6- and ~20-fold, respectively). ATR-FTIR linked species-specific susceptibility to cell-wall architecture. SEM confirmed membrane destabilization and perforation. In MDA-MB-231, necrotic fractions reached ~9% and >40% for Ag-ZnO and Cu-ZnO, respectively. Both metal oxide nanocomposites (MONCs) act through ion release, revealing a selectivity window, especially for Ag-ZnO. Further studies on non-cancerous cells, ion-release kinetics, uptake and in vivo validation are essential to establish a therapeutic index. Full article

Background/Objectives: Wound infections represent a major clinical challenge due to their polymicrobial nature, biofilm formation, and increasing antimicrobial resistance, which compromise conventional treatments. This study aimed to develop and evaluate ligand-stabilized silver nanoparticles (AgNPs) with improved antimicrobial activity and cytocompatibility, and to investigate their incorporation into electrospun nanofibers for wound management. Methods: Four AgNP formulations stabilized with citrate, cysteine, ketorolac, and diclofenac were synthesized via chemical reduction. Physicochemical characterization included surface plasmon resonance and zeta potential measurements. Antimicrobial activity was assessed through minimum inhibitory concentration (MIC) and bactericidal assays against Gram-positive, Gram-negative, and fungal strains. Toxicity was evaluated using the HET-CAM assay, while cytocompatibility was determined in fibroblasts, MG-63 cells, and mesenchymal stem cells. Diclofenac-stabilized AgNPs were incorporated into electrospun PCL/PEO nanofibers to generate a functional nanocomposite system. Results: All AgNPs exhibited a characteristic SPR at ~400 nm and high colloidal stability. Diclofenac-stabilized AgNPs (dc-AgNPs) showed the highest antimicrobial activity, with MIC values of 18.8 mg/L against Staphylococcus aureus and Pseudomonas aeruginosa, and 4.7 mg/L against Candida albicans, along with strong bactericidal effects. HET-CAM assays indicated negligible irritation at concentrations up to 75 mg/L. Cytocompatibility results revealed a dose-dependent response, with fibroblasts being more sensitive. Electrospun nanofibers loaded with dc-AgNPs achieved a 2.6 log reduction against Streptococcus mutans and moderate reductions (0.4–0.7 log) against other pathogens. Conclusions: Ligand engineering critically influences the antimicrobial efficacy and biocompatibility of AgNPs. The incorporation of dc-AgNPs into electrospun nanofibers represents a promising approach for treating biofilm-associated wound infections. Full article

Polyphenolic compounds extracted from Taraxacum officinale (dandelion) were used as natural chelating ligands to synthesize copper–polyphenol complexes, which were subsequently immobilized on sericite to obtain hybrid organic–inorganic materials. The complexes were prepared under controlled pH and temperature conditions, yielding structures with different Cu–polyphenol ratios. Structural characterization confirmed the formation of Cu(II)–polyphenol chelates, partial reduction to Cu(I) species at higher pH values, and the deposition of mixed Cu₂O/CuO phases on the layered sericite substrate. Copper–polyphenol superstructures, copper nanoparticles, and copper oxide crystallites were heterogeneously distributed depending on synthesis conditions and metal–ligand ratios. The hybrid materials exhibited modified optical properties, combining the intrinsic reflectance of sericite with UV absorption from polyphenols and copper species. When incorporated into an emulsion matrix, the materials showed promising UV-screening performance, with SPF-equivalent values ranging from 7 to 33 depending on concentration. Antimicrobial evaluation demonstrated that copper–polyphenol complexes displayed enhanced activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Candida albicans compared to the natural extract, while sericite-supported hybrids retained selective efficacy, particularly against Gram-positive bacteria and C. albicans. These results indicate the potential of dandelion-derived copper complexes and their sericite hybrids as multifunctional bioactive agents for cosmetic dermatology applications. Full article

The chemical composition and bioactivities of dry methanol extracts from roots, leaves and fruits of Prangos trifida (Apiaceae), collected in Serbia, were investigated. LC-DAD-QTOF-MS/MS analysis revealed 30 compounds, primarily polyphenols and coumarins. The root and leaf extracts were rich in chlorogenic and/or 3,5-di-O-caffeoylquinic acid (18.20–26.14 mg/g extract), and the fruit extract in oxypeucedanin hydrate and prantschimgin (46.50 and 71.64 mg/g). The leaf extract exhibited the highest total phenolic content (62.86 mg quercetin equivalents/g), total antioxidant activity (FRAP = 0.71 mmol Fe²⁺/g) and DPPH radical scavenging ability (44.08 mg quercetin equivalents/g). Antimicrobial activity testing (11 bacteria and three yeasts, microdilution method) showed that the most active were the root and leaf extracts against Micrococcus luteus, Staphylococcus aureus, S. epidermidis and Candida albicans (MIC = 0.625–5 mg/mL). The fruit extract showed the strongest cytotoxicity against tested stomach, colon and hypopharynx cancer cell lines (MTT test), with the highest selectivity toward hypopharynx cancer FaDu cells (selectivity index 4.71; determined in relation to non-cancerous VERO cells). No antiviral activity against herpesvirus type 1 was found. The results indicate that P. trifida represents a promising source of polyphenols and coumarins, notably expanding current knowledge on its chemical composition and supporting its potential relevance for pharmaceutical and food industry applications. Full article

Mucormycosis is a devastating invasive fungal infection primarily caused by Mucor and Rhizopus species, presenting significant clinical challenges due to limited therapeutic options and emerging drug resistance in opportunistic yeasts such as Candida albicans. This study explores foliar endophytic fungi from Thai medicinal plants as potential reservoirs for novel bioactive metabolites targeting both fungal growth and virulence factors. We report the first isolation of Fusarium proliferatum as an endophyte from Lantana camara L. foliage (voucher number 01562), with its identity confirmed through morphological characterization and sequencing of the fungal ITS4/ITS5 regions. Antifungal susceptibility testing showed potent activity against a panel of environmental Mucorales, with minimum inhibitory concentrations (MICs) ranging from 0.3 to 1 mg/L. In dual-culture assays, F. proliferatum demonstrated significant mycelial inhibition rates of 93.30% to 93.67% against Mucor spp. and 88.67% to 93.67% against Rhizopus spp. Furthermore, the crude extract exhibited a potent anti-virulence effect by suppressing the C. albicans yeast-to-hyphal transition, achieving up to 68% germination inhibition in resistant strains. Liquid chromatography–mass spectrometry (LC-MS) analysis identified 51 secondary metabolites, including the cyclic peptide beauvericin and various polyketides and indole derivatives. These findings suggest that F. proliferatum utilizes metabolic mimicry and adaptive synergy with its host plant to produce a diverse chemical arsenal. This study positions foliar endophytes of L. camara as promising candidates for the development of dual-action therapeutics to combat invasive and resistant mycoses. Full article

The mitochondrial membrane protein UPS1, a conserved intermembrane space protein in Saccharomyces cerevisiae, possesses phosphatidic acid transfer activity and plays a positive regulatory role in processes such as cardiolipin metabolism and transport. The role of UPS1 protein in pathogenic fungi such as Candida albicans has not been explored, especially in relation to its influence on virulence factors like hyphal growth and biofilm formation, which are crucial for the pathogenicity of C. albicans. The research investigated the function of the UPS1 protein in C. albicans by using gene knockout techniques, analyzing mitochondrial function, and conducting tests for hyphal and biofilm development. The results revealed that deletion of the UPS1 gene leads to altered mitochondrial morphology, increased reactive oxygen species levels, and reduced intracellular ATP content, thereby causing severe growth defects in C. albicans. In addition, transcriptomic analysis indicated that loss of UPS1 significantly represses the expression of genes associated with hyphal growth and biofilm formation. Functional assays further confirmed that UPS1 deficiency markedly impairs cell adhesion capability, hyphal development, and biofilm formation of C. albicans. Notably, deletion of the UPS1 protein markedly reduces the susceptibility of C. albicans to membrane-targeted antifungal drugs. Finally, infection models using Galleria mellonella larvae and a murine vulvovaginal candidiasis model verified that UPS1 gene knockout attenuates the pathogenicity of C. albicans. In summary, our findings demonstrate that UPS1 protein modulates the pathogenicity of C. albicans by regulating mitochondrial function, hyphal growth, and biofilm formation. Full article

Background/Objectives: Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-related morbidities. Also, severe clinical outcomes derived from CAUTIs demand an urgent need for the development of novel antimicrobial catheter materials. Since CAUTIs are primarily driven by a wide range of microorganisms causing biofilm formation on the surfaces of catheters, evaluating the effectiveness of innovative antimicrobial materials against a broad spectrum of known uropathogens is warranted. We aim (1) to demonstrate the ability of incorporated organo-selenium versus that of an FDA-cleared antimicrobial catheter and (2) to show that the results of the study are consistent against the most common microorganisms causing urinary tract infections in humans. Methods: Based on encouraging preliminary studies, three percent of organo-selenium (weight-based), as a novel antimicrobial catheter material, was incorporated into thermoplastic polyurethane (TPU). This was compared in vitro with plain polyurethane catheters and the SILQ ClearTract catheter with a zwitterionic coating (FDA-cleared for its antimicrobial properties in December 2022). The antimicrobial activity was studied against Candida albicans, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, MRSA, and Staphylococcus epidermidis by assessment of colony-forming unit counts along with visual confirmation using Scanning Electron Microscopy (SEM). Results: Plain polyurethane catheters (control group) showed 7- to 8-log of in vitro growth for all tested microbes, whereas the antimicrobial zwitterionic SILQ ClearTract catheters still showed 6- to 7-log of microbial growth. In contrast, organo-selenium-incorporated catheters demonstrated no detectable in vitro growth for all tested microbes (C. albicans, E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, S. aureus, MRSA, and S. epidermidis). SEM analysis also validated the findings. Conclusions: Potentially non-leaching organo-selenium, as a novel urinary catheter material, significantly inhibited microbial attachment, growth, and biofilm formation across a wide spectrum of common uropathogenic organisms compared to a zwitterionic catheter, providing a strong foundation for further detailed in vivo and clinical studies. Full article

Cervicovaginal dysbiosis is an established co-factor of high-risk human papillomavirus (HPV) persistence and cervical neoplastic development, yet most studies address the bacterial compartment in isolation, leaving fungal communities and bacterial–fungal cross-kingdom interactions underexplored, particularly in Central Asian populations. We performed shotgun metagenomic sequencing (mNGS) of cervicovaginal samples from 311 Kazakhstani women undergoing routine cervical screening. HPV status was determined using combined PCR and mNGS methods, and cervical screening was completed using liquid-based cytology (NILM, ASC-US, LSIL, ASC-H). Bacterial, viral, and fungal taxa were profiled from a single shotgun dataset with Kraken2 pipeline. Bacterial community state types (CSTs) were determined based on dominant bacterial species, functional gene content was annotated against KEGG using eggNOG, and covariate-adjusted associations were estimated using MaAsLin3. Mycobiome β-diversity differed significantly by HPV status (p = 0.003). In particular, Candida positivity was significantly associated with HPV presence and with high-risk α-9 HPV in cytologically normal (NILM) samples (OR = 3.6, [1.6–9.6], p ≤ 0.001). Covariate-adjusted analysis was consistent with this positive association (q < 0.05). Concurrently, among CSTs, Lactobacillus iners-dominated CST III and dysbiotic Gardnerella vaginalis-dominated CST IV showed a 3-fold higher Candida albicans prevalence (p < 0.01). Further analysis demonstrated that, functionally, both of these CSTs had depleted capacity for lactate metabolism (ko00620, p < 0.0001) and, in particular, for the genetic capacity for pyruvate-dependent H₂O₂ generation (half that of the L. crispatus-dominated CST I). These findings support L. iners as a metabolically permissive rather than protective Lactobacillus and suggest cross-kingdom functional signatures as candidate biomarkers for HPV acquisition and persistence in Central Asia, a region previously absent from the cervicovaginal microbiome literature. Full article