Search Results (971)

Background/Objectives: Cutaneous leishmaniasis (CL) remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and emerging resistance. Repurposing azole antifungals is a promising approach, as they target ergosterol biosynthesis, a pathway also essential in Leishmania spp. This study investigated the antileishmanial potential of econazole through in vitro and in vivo assays. Methods: Econazole activity was evaluated against Leishmania amazonensis promastigotes and intracellular amastigotes using MTT and luminescence-based methods. Cytotoxicity in NCTC cells was determined to calculate the selectivity index (SI). Drug interactions with miltefosine were assessed by fixed-ratio isobologram analysis. In vivo efficacy was examined in BALB/c mice infected with L. amazonensis and orally treated with econazole (2.5, 5, or 10 mg/kg/day) for 28 days. Lesion development and parasite burden were monitored. Molecular docking simulations were performed using SwissDock. Results: Econazole showed potent in vitro activity, with EC₅₀ values of 8.9 µM for promastigotes and 11 µM for intracellular amastigotes, and a CC₅₀ of 31 µM. Isobologram analysis revealed additive interactions with miltefosine (ΣFIC 0.5–1.2; mean 0.95). In vivo, econazole reduced lesion size and parasite load, achieving up to 75% reduction at 10 mg/kg/day. Docking results suggested that econazole may inhibit sterol biosynthesis, potentially through interaction with 14α-demethylase. Conclusions: These findings provide the first evidence of econazole activity against L. amazonensis in vitro and in vivo. Its exploratory efficacy and compatibility with miltefosine support further investigation of econazole as a repurposed candidate for CL, including optimization of dosing strategies and combination regimens. Full article

In this study, we created multifunctional bone tissue engineering scaffolds that combine prophylactic antifungal action with structural support. We produced PVA/CS/HA/BA nanofiber matrices via a specifically designed electrospinning technique to stop early cross-linking. Through SEM, our examination of fiber shape revealed diameters ranging from 178 ± 53 nm to 330 ± 69 nm. We discovered that this variation was closely correlated with the Boric Acid (BA) level. Our EDS and FTIR studies further showed that HA and BA were effectively mixed, with a specific focus on the production of borate-ester linkages inside the network. Mechanical examination revealed that 0.25 wt.% BA maximizes the tensile strength at 9.15 MPa, thereby closely matching HA-reinforced standards, while HA incorporation improved thermal stability. Moreover, in vitro hFOB experiments showed sustained cytocompatibility at 0.25 wt.% BA. While 0.5 wt.% BA showed strong antifungal action against Candida albicans, it sadly harmed cell viability. The 0.25 wt.% BA concentration ultimately offers a better balance between mechanical integrity and antibacterial action, therefore presenting a potential method for scaffold generation for bone regeneration in immunocompromised patients. Full article

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such as cardiotoxicity, associated with impurities like RT6 (albonoursin). The fundamental analytical techniques for quality control are outlined. Furthermore, the clinical applications and combination therapy strategies of nystatin in treating oral diseases, vaginitis, and otitis externa are summarized in detail. Regarding biosynthesis, the assembly mechanism of nystatin A₁ via the type I polyketide synthase pathway and its subsequent modification processes are thoroughly discussed. Emphasis is placed on the latest advances and potential of gene-editing technologies, particularly CRISPR/Cas9, in the targeted knockout of genes responsible for toxic components and in optimizing production strains to enhance nystatin yield and purity. Finally, this review prospects the future development of nystatin towards improved safety and efficacy through structural optimization, innovative delivery systems, and synthetic biology strategies, aiming to provide a reference for its further research and clinical application. Full article

Candidozyma auris (previously named Candida auris) has been recognized as a significant public health threat due to its extensive transmission in hospital settings, high mortality rates, and multidrug resistance. Evidence regarding optimal antifungal treatment in children remains limited. The present systematic review aims to synthesize available evidence on pediatric C. auris infections, focusing on antifungal treatment, resistance profiles, and clinical outcomes. A systematic search was conducted across PubMed, Scopus, and Web of Science, identifying case reports and case series of pediatric patients with confirmed C. auris infection. Data were extracted on demographics, comorbidities, infection site, antifungal therapy, and outcomes. Risk of bias was assessed using JBI Critical Appraisal checklists. Fourteen studies comprising 62 patients were included, with most cases being bloodstream infections. C. auris showed widespread fluconazole resistance and variable susceptibility to amphotericin B. Echinocandins were the most commonly used agents, generally associated with survival. Overall mortality was 35%, similar to that reported for adults. Combination therapy showed numerically higher survival, although given the small sample size and heterogeneity of treatment regimens, no comparative inferences can be made. Pediatric C. auris infections mirror adult patterns of antifungal resistance and mortality. Echinocandins remain first line therapy; however, the emergence of echinocandin resistance underscores the urgent need for antifungal stewardship, standardized pediatric guidelines, and novel antifungal development. Full article

Biofuel cells (BFCs) generate electricity by converting chemical energy into electrical energy using biological systems. Saccharomyces cerevisiae (yeast) is an attractive biocatalyst for BFCs due to its robustness, low cost, and metabolic versatility; however, electron transfer from the intracellular reactions to the electrode is limited by the cell membrane. Nystatin is an antifungal antibiotic that increases the permeability of fungal membranes. We hypothesized that sub-lethal nystatin treatment could enhance mediator-assisted electron transfer without compromising cell viability. In this work, yeast was treated with nystatin during cultivation at concentrations of up to 6 µg/mL and combined with a dual-mediator system consisting of a lipophilic mediator (9,10-phenanthrenequinone, PQ) and a hydrophilic mediator (potassium ferricyanide). Scanning electrochemical microscopy revealed that the dual-mediator system increased local current responses by approximately fivefold compared to a single mediator (from ~11 pA to ~59 pA), and that nystatin-treated yeast exhibited higher local electrochemical activity than untreated yeast (maximum currents of ~0.476 nA versus ~0.303 nA). Microbial fuel cell measurements showed that nystatin treatment increased the maximum power density from approximately 0.58 mW/m² to approximately 0.62 mW/m² under identical conditions. Nystatin concentrations between 4 and 5 µg/mL maintain yeast viability at near-control levels, while higher concentrations cause a decrease in viability. These results demonstrate that controlled, sub-lethal membrane permeabilization combined with a dual-mediator strategy can enhance electron transfer in yeast-based biofuel cells. Full article

Rhododendron tomentosum is an aromatic plant belonging to the Ericaceae family, widely used for different applications, but still lacking in its molecular signature. This work provides a complete chemical and biological characterization of the hydroalcoholic extract of R. tomentosum tips of twigs. Combining untargeted metabolomic analysis with bioassays, a correlation between chemical composition and biological activity was defined. To this regard, liquid chromatography high-resolution tandem mass spectrometry (LC-MS/MS) revealed a heterogeneous chemical composition, including flavonoids, such as quercetin, catechin, and their derivatives, as well as a first tentative identification of novel aesculin derivatives. Cell-based model experiments on stressed immortalized human keratinocytes demonstrated the antioxidant activity of the extract. Moreover, it exhibited significant antifungal and antibacterial effects against Trichoderma atroviride AGR2, Botrytis cinerea, and Clavibacter michiganensis, while promoting the growth of the beneficial bacterium Bacillus amyloliquefaciens. These findings highlight the rich diversity of bioactive molecules present in R. tomentosum hydroalcoholic extract, bridging its chemical composition to its functional properties. Overall, these results suggest its promising potential for applications in improving plant health, as well as in pharmaceutical, cosmetic, and agricultural industries. Full article

Background: In the last decade, infections caused by Candida species have increased. Although C. albicans remains the most predominant species, fungal infections caused by non-albicans Candida (NAC) species have also been rising. This study aimed to determine which Candida spp. are most frequently associated with oral candidiasis. Methods: In accordance with PRISMA guidelines, a literature search was conducted in the PubMed, Cochrane Library, and ScienceDirect databases. The search used the keyword combination “candida spp” AND “oral candidiasis” AND “oral isolates” and included articles published between 2013 and 31 October 2025. Results: A total of 658 articles were identified, of which 24 met the inclusion criteria. Across these studies, 12,750 isolates were reported. C. albicans was the most prevalent species, accounting for 81.7% of all isolates. NAC species were detected at lower frequencies, including C. tropicalis (7.2%), C. glabrata (4.5%), C. krusei (4.1%), C. parapsilosis (1.0%), C. dubliniensis (0.8%), C. kefyr (0.2%), C. guilliermondii (0.1%), C. lusitaniae (0.1%), and other rare or unidentified species (0.2%). The increasing prevalence of Candida infections is associated with a growing population of immunocompromised individuals, and treatment remains challenging due to rising antifungal resistance. Conclusions: Although C. albicans remains the most prevalent, the appearance of NAC species is gradually increasing. With the increase of Candida spp. resistant to conventional antifungal agents and with the competitive or synergistic interaction between Candida spp., it is necessary to develop new therapeutic approaches. Full article

The rising global incidence of Candida parapsilosis infections is increasingly complicated by antifungal resistance, resulting in frequent therapeutic failure. This study investigated the potential of the natural compound catechin to enhance the efficacy of fluconazole through synergistic interaction. We evaluated the susceptibility of C. parapsilosis clinical isolates and a reference strain to combinations of catechin and fluconazole using standardized microbiological assays and molecular techniques. In vivo efficacy was assessed using the Galleria mellonella infection model. Mechanistic studies included the measurement of intracellular reactive oxygen species (ROS) production and plasma membrane permeability. Catechin alone caused growth retardation in all strains. However, the combination of catechin and fluconazole resulted in complete growth inhibition of the reference strain and significant growth reduction in azole-resistant clinical isolates. While the combination slightly increased intracellular ROS production, no significant changes in plasma membrane permeability or membrane potential were observed. Notably, catechin induced the expression of the resistance-associated genes CpTAC1 and CpCDR1B in resistant isolates. In vivo experiments demonstrated that catechin significantly reduced mortality in G. mellonella larvae infected with C. parapsilosis. These findings suggest that catechin is a promising candidate for developing synergistic antifungal therapies against resistant Candida species. Full article

Background/Objectives: Fingernail onychomycosis differs etiologically and epidemiologically from toenail infections and is frequently complicated by colonization and mixed growth. Reliable interpretation of microscopy–culture correlations is essential for avoiding overdiagnosis and guiding therapy. This study aimed to characterize the diagnostic structure, species distribution, and antifungal susceptibility patterns of fingernail onychomycosis in a large routine-laboratory cohort, and to evaluate the performance of a five-tier operational classification integrating microscopy and semi-quantitative culture. Methods: Laboratory records from 1075 patients with clinically suspected fingernail onychomycosis (including nail and periungual samples) were analyzed retrospectively (2017–2024). Direct microscopy with calcofluor white, semi-quantitative culture, and MALDI-TOF MS identification were performed. Cases were categorized based on predefined criteria combining microscopic elements with colony quantity and purity. Species distribution, age–sex patterns, diagnostic concordance between microscopy and culture, and results of EUCAST broth microdilution testing for selected yeasts were assessed. Results: The overall proportion of mycologically positive cases was similar in women and men, although age-dependent patterns differed. Microscopic findings correlated with culture outcomes, with hyphae predicting dermatophytes, yeast cells predicting ascomycetous yeasts, and negative slides aligning with the absence of growth. Yeasts predominated (Candida parapsilosis 30.9%, C. albicans 18.5%), dermatophytes were mainly Trichophyton rubrum, and molds were uncommon. Periungual swabs showed species distributions closely matching those from nail samples and demonstrated high analytical concordance. EUCAST MICs revealed species-dependent variation, including elevated amorolfine MICs in C. parapsilosis and reduced fluconazole activity in Wickerhamomyces pararugosa. Conclusions: Fingernail onychomycosis in this cohort was predominantly yeast-associated, with predictable microscopy–culture relationships and distinct age–sex patterns. The five-tier operational framework improved classification of infection versus colonization, and is proposed as a preliminary tool requiring clinical validation, while contemporary MIC data highlighted clinically relevant interspecies differences. The absence of clinical correlation data (symptoms, severity, treatment history) remains the primary limitation, preventing definitive distinction between infection and colonization in all cases. Full article

Fungal pathogens, including Colletotrichum gloeosporioides and Pestalotiopsis spp., are significant threats to global cacao production. Understanding their varying responses to novel antifungal agents is crucial for developing sustainable plant protection strategies. This study investigated the quantitative morphological responses and isolate-specific sensitivity of three cacao pathogen isolates (one Pestalotiopsis sp. and two C. gloeosporioides) to four novel bio-based phenolic-branched fatty acids and their corresponding amides derived from renewable feedstocks. We observed a high degree of isolate-specific susceptibility. A phenol-branched soy oil-derived fatty amide (PhSOAM) proved most potent, significantly inhibiting the growth of Pestalotiopsis sp. and one C. gloeosporioides isolate. In contrast, the second C. gloeosporioides isolate displayed complete insensitivity to all tested compounds, highlighting significant intraspecific variation. Notably, quantitative image analysis revealed that PhSOAM uniquely altered fungal colony morphology by significantly increasing the length-to-width ratio, suggesting a mechanism of action involving the disruption of polarized growth. Multivariate analyses and machine learning models (R² up to 0.74) effectively classified these responses, identifying the specific pathogen-compound pairing as the most critical determinant of the interaction outcome. This work not only highlights the potential of bio-based amides but also establishes a powerful analytical framework, combining morphological profiling with predictive modeling, to gain deeper insights into the complex, isolate-specific nature of fungal–antifungal interactions. Full article

Botrytis cinerea Pers., the causal agent of grey mould, causes major economic losses in viticulture by reducing grape and wine quality and yield. Antagonistic yeasts that release bioactive volatile organic compounds (VOCs) represent a sustainable alternative to synthetic fungicides. Here, VOCs produced by Pichia guilliermondii strain ZIM624 were identified and assessed for antifungal activity against B. cinerea. 65 VOCs—including higher alcohols, volatile phenols, esters, and terpenes—were detected using two newly developed and validated analytical methods combining automated headspace solid-phase microextraction with gas chromatography–mass spectrometry. A total of 13 VOCs were selected for the bioassays. Fumigation assays demonstrated that terpenes (citronellol, geraniol, nerol, α-terpineol, and linalool) were the most effective inhibitors of B. cinerea mycelial growth (EC₅₀ = 6.3–33.9 μL/L). Strong inhibition was also observed for 4-vinylphenol and isoamyl acetate. In vivo assays confirmed that exposing infected grape berries to P. guilliermondii VOCs significantly reduced grey mould incidence. These results highlight the potential of P. guilliermondii ZIM624 volatiles as natural biofumigants for the eco-friendly management of B. cinerea in grapes. Future research should focus on optimising VOC production, evaluating efficacy under field conditions, and developing formulations for practical application in vineyards and post-harvest storage. Additionally, investigating potential synergistic effects of VOC combinations could lead to more effective biocontrol strategies. Full article

Cutaneous infections caused by dematiaceous fungi are rare in the general population but are increasingly recognized in solid organ transplant recipients as a consequence of prolonged immunosuppression. When Alternaria species are confirmed as the causative agents of a skin infection, the condition is referred to as alternariosis. These infections may clinically resemble bacterial or neoplastic lesions and require accurate diagnosis and individualized therapy. We report one case of cutaneous alternariosis in a kidney transplant recipient receiving tacrolimus-based immunosuppression. The patient was a 47-year-old woman who sustained minor trauma to her knee three months after transplantation. She developed an ulcerated, crusted lesion, which coincided with severe neutropenia. Histology, culture and molecular identification confirmed A. infectoria. Treatment included systemic azole therapy (voriconazole followed by isavuconazole) and surgical excision, resulting in resolution without recurrence. This case highlights the importance of early recognition of alternariosis in transplant recipients. Successful management typically requires combined surgical and systemic antifungal therapy, with careful monitoring of drug interactions and immunosuppressive levels to prevent toxicity or rejection. Full article

This study explored an eco-friendly coating system combining seagrass-derived cellulose fiber (SCF) from Cymodocea rotundata with marine type I collagen (MC) for tomato preservation. The SCF/MC composite was prepared through enzymatic and natural crosslinking processes and subsequently characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), and thermogravimetric analysis (TGA). The results demonstrated that SCF/MC possessed a compact morphology, strong hydrogen bonding interactions, high crystallinity, and excellent thermal stability. When applied as a coating, SCF/MC composite significantly reduced weight loss in tomatoes, preserved firmness (>39 Units), regulated acidity, maintained moisture levels (~90%), and delayed increase in pH compared to the uncoated control. Additionally, the SCF/MC coating sustained ascorbic acid and moderated lycopene accumulation, indicating delayed ripening. At 0.5% of SCF/MC composite, spoilage was limited to 22% versus ~80% in control samples, demonstrating a substantial reduction in decay. Antifungal assay showed strong inhibition of Aspergillus flavus, with the highest suppression of mycelial growth observed at 0.5% of SCF/MC. Overall, the SCF/MC coating effectively enhanced fungal safety and maintained the physicochemical quality of tomatoes, thereby extending shelf life while valorizing seagrass biomass as a sustainable postharvest resource. Full article

(1) Background: Oat (Avena sativa L.) is a crop that is widely used in human nutrition, while it also plays an important role in animal husbandry as a high-quality forage crop. However, this crop is particularly susceptible to combined biotic stressors, including insect pests (Agriotes lineatus) and fungal infections (Fusarium spp.). These stresses act synergistically: root damage caused by wireworms increases the plant’s susceptibility to fungal infection, while pathogens further limit nutrient uptake and root system development. In recent years, the reduced efficacy of chemical pesticides against both insect pests and fungal pathogens has highlighted the need for alternative strategies in oat protection, leading to an increased focus on developing bacterial bio-inoculants as sustainable and effective biocontrol agents. (2) Methods: This study aimed to identify bacterial strains capable of suppressing wireworms (Agriotes lineatus) and Fusarium spp. in oats, while simultaneously promoting plant growth. Bacterial isolates were screened for key Plant Growth Promoting (PGP) and biocontrol traits, including IAA and siderophore production, phosphate solubilization, and the presence of toxin- and antibiotic-coding genes. (3) Results: The highest insecticidal effect against wireworms was recorded for Bacillus velezensis BHC 3.1 (63.33%), while this isolate also suppressed the growth of F. proliferatum for 59%, F. oxysporum for 65%, F. poae for 71%, and F. graminearum for 15%. The most effective Bacillus strains (with insecticidal and antifungal activity) were identified and tested in two pot experiments, where their ability to enhance plant growth in the presence of insects and fungi was evaluated under semi-controlled conditions. An increase in plant biomass, grain yield, and nitrogen content was observed in oat inoculated with B. velezensis BHC 3.1 and B. thuringiensis BHC 2.4. (4) Conclusions: These results demonstrate the strong potential of both strains as multifunctional bio-inoculants for enhancing oat growth and mitigating the adverse effects of wireworm damage and Fusarium infection. Full article

Background/Objectives: Mucormycosis is a rapidly progressive invasive fungal infection that commonly involves the sinonasal region and skull base in patients with systemic comorbidities, yet robust ENT data from middle-income settings are scarce. Methods: We performed a single-center retrospective review of all patients with histopathologically confirmed mucormycosis treated in the Otorhinolaryngology Department of Dicle University between 2010 and 2023, covering a 14-year period. Eligible patients had paranasal sinus computed tomography at presentation and received surgical and/or systemic antifungal therapy. Demographic data, comorbidities, disease subtype, radiological extent, treatment modality and survival were extracted from records. Survival was estimated using Kaplan–Meier analysis, and group differences were tested with chi-square statistics (p ≤ 0.05). Results: Fifty-two patients met the inclusion criteria (mean age 56.5 ± 15.2 years; 57.7% male); 73.1% had at least one systemic comorbidity, most frequently diabetes mellitus (65.4%) and hematological malignancy (19.2%). Disease was sinonasal in 42.3%, rhino-orbital in 28.8% and rhino-orbito-cerebral in 28.8%. Baseline CT showed intracranial extension in 26.9%. Overall survival was 59.6% and differed markedly by subtype, highest in isolated sinonasal disease (81.8%) and lowest in rhino-orbito-cerebral disease (26.7%). Intracranial extension was associated with higher mortality (71.4% vs. 28.9%). Combined surgical debridement plus systemic antifungal therapy, used in 84.6% of patients, yielded lower mortality than antifungal therapy alone (31.8% vs. 87.5%). Conclusions: In this ENT cohort, prognosis was mainly determined by anatomical extent and treatment strategy. Our findings suggest that timely combined surgical and antifungal management, when feasible and in appropriately selected patients, is associated with improved survival outcomes. Full article