Search Results (2,478)

Invasive fungal infections can be life-threatening, particularly in patients with impaired immunity, yet treatment remains limited to a few antifungal drug classes. During infection, fungal pathogens encounter changes in temperature, nutrient availability, immune pressure and drug exposure that challenge their growth and survival. tRNA modifications may contribute to adaptation by supporting tRNA stability, aminoacylation and codon decoding. Studies in Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans have linked conserved tRNA-modification pathways to fungal development, host interaction, stress adaptation, virulence and the response to 5-fluorocytosine, with evidence ranging from genetic and infection phenotypes to biochemical characterization of modification reactions. In this Review, we examine how these studies connect modification chemistry and substrate tRNAs with translation, protein output and infection phenotypes. We also draw on mechanistic studies from model organisms and plant-pathogenic fungi to clarify translational links that remain unresolved in human fungal pathogens. We conclude by discussing when tRNA-modification pathways become functionally limiting under host-associated conditions and how they may alter antifungal responses. Full article

From a health perspective, the 21st century has witnessed the emergence and global impact of several major viral diseases, most notably coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, which has been associated with a substantial burden of secondary fungal infections. Patients suffering from COVID-19 illnesses frequently developed fungal co-infections, which can worsen clinical outcomes and complicate therapeutic efforts. Hospitalized individuals with viral infections are particularly susceptible to invasive fungal pathogens, including Aspergillus, Candida, and Mucorales species. The co-pathogenesis between respiratory virus and fungi is complex, involving dynamic interactions among the pathogens and the host immune system. Opportunistic fungal infections were found to be more prevalent in COVID-19-infected individuals, who require mechanical ventilation, have diabetes, or exhibit neutropenia. This review aims to provide a comprehensive overview of fungal co-infections associated with COVID-19 disease, with a focus on their pathogenesis, biomarkers, diagnostic approaches, and potential treatment strategies. Overall, the available evidence indicates that viral-induced immune dysregulation, epithelial barrier damage, and clinical risk factors contribute to the development and severity of fungal co-infections in COVID-19 patients. Early recognition using reliable biomarkers and standardized diagnostic approaches, together with timely and pathogen-directed antifungal therapy, are essential for improving clinical outcomes. Full article

The excessive use of fungicides in agriculture has generated environmental problems, increased resistance in plant pathogenic fungi, and raised concerns for food safety and human health. This study evaluates silver-based nanoparticles (NPs) as a potential alternative for the control of plant pathogens. Ag₂S-S Janus and AgNPs were synthesized through chemical reduction using non-toxic compounds, employing glucose as a reducing agent (0.30 and 0.90%) and gelatin as a passivating agent (0.50 and 1.00%), generating four treatments. The synthesized NPs showed average sizes ranging from 5 to 11 nm, with the smallest particles obtained in treatment T3 (5.90 ± 0.30 nm) and the largest in T4 (10.34 ± 0.46 nm). The antifungal and anti-oomycete activity of the NPs was evaluated in vitro against four microorganisms: Alternaria alternata, Colletotrichum boninense, Fusarium oxysporum, and Phytophthora capsici. Results showed complete inhibition (100%) of A. alternata and 60–70% inhibition of P. capsici in all treatments, demonstrating strong antimicrobial potential. Additionally, NPs were applied to tomato seedlings (Solanum lycopersicum) inoculated with Fusarium oxysporum f. sp. lycopersici. NPs were not phytotoxic and reduced disease severity (on a 1–2 scale) while promoting lesion healing. Full article

Background: Disseminated invasive aspergillosis (IA) is an uncommon but devastating manifestation of disease, particularly when the central nervous system (CNS) is involved. The clinical features and outcomes of CNS dissemination, compared with isolated invasive pulmonary aspergillosis (IPA) and other disseminated forms, remain poorly characterized. Methods: Using an institutional database of 1157 cancer patients diagnosed with IA between 1993 and 2024, we identified 43 patients with disseminated IA, defined as infection involving ≥2 non-contiguous organ systems, including 8 with CNS involvement. Patients with disseminated IA were matched 1:3 to patients with IPA based on year of diagnosis. We compared clinical features, antifungal treatment, and outcomes between: (1) CNS-disseminated IA and IPA, and (2) CNS-disseminated IA and other forms of disseminated IA. Results: Baseline characteristics, including hematologic malignancy subtype, hematopoietic stem cell transplantation status, neutropenia, and antifungal prophylaxis, were similar across groups. Aspergillus fumigatus was the predominant species in all cohorts. No patients with CNS-disseminated IA achieved clinical response at end of therapy, versus 35% with IPA (p = 0.05) and 30% with other disseminated IA (p = 0.17). Twelve-week IA-associated mortality was significantly higher in CNS-disseminated IA than in IPA (88% vs. 45%, p = 0.028) and was higher than in other disseminated IA (88% vs. 46%, p = 0.05). Combination antifungal therapy was more frequently used in CNS-disseminated IA than in IPA (63% vs. 31%) and other disseminated IA (63% vs. 43%), while rates of ICU admission and mechanical ventilation were similar across groups. Conclusions: CNS involvement in disseminated IA defines a distinct, high-risk phenotype, with profoundly reduced treatment response and survival despite comparable baseline characteristics. Given the small number of CNS cases and the predominance of cases diagnosed during earlier study periods, these findings should be interpreted with caution. Although combination antifungal therapy was used more frequently in CNS-disseminated IA, no significant outcome benefit was observed, underscoring the need for improved therapeutic approaches for CNS aspergillosis in immunocompromised hosts. Full article

Background/Objectives: Cutaneous fungal infections remain a major therapeutic challenge due to poor skin penetration and emerging antifungal resistance of current treatments. Drug repurposing offers a promising strategy to expand antifungal therapy, with ketoprofen (KPN) recently demonstrating antifungal activity. Methods: In this study, KPN-cationic aspasomes (Ca-ASPMs) were developed using a Quality by Design (QbD) approach to enhance topical delivery and maximize the therapeutic potential of repurposed KPN. A D-optimal experimental design was implemented to investigate the influence of ascorbyl palmitate amount (X₁), ethanol concentration (X₂), and cationic SAA type (X₃) on the critical quality attributes of KPN-Ca-ASPMs, namely entrapment efficiency, particle size, and zeta potential. Results: Numerical optimization identified an optimum formulation comprising 10 mg ascorbyl palmitate, 5% ethanol, and didodecyldimethylammonium bromide (DDAB) as cationic SAA, with an overall desirability of 0.815. The optimal KPN-Ca-ASPM (F9) exhibited nanosized vesicles (213.24 ± 2.20 nm) and 91.30 ± 10.01% entrapment efficiency. TEM confirmed the spherical morphology of the vesicles, while DSC demonstrated successful incorporation of KPN within the aspasomal matrix. F9 exhibited enhanced in vitro drug release (68% after 6 h) and excellent storage stability. Confocal laser scanning microscopy demonstrated enhanced skin penetration of F9. In a murine cutaneous candidiasis model, F9 significantly enhanced the antifungal efficacy of KPN, producing a 2.989-log reduction in fungal burden compared with the untreated group and significantly outperforming the free drug (p = 0.0005). Histopathological examination confirmed restoration of normal skin architecture. Conclusions: Collectively, the QbD-guided development of KPN-Ca-ASPM provided a reproducible nanocarrier that significantly enhanced the topical antifungal efficacy of repurposed KPN, highlighting its potential for the treatment of cutaneous candidiasis. Full article

Globally, invasive fungal diseases are increasing in incidence and are associated with high rates of mortality. A lack of effective diagnostic protocols, antifungal resistance and poor antifungal stewardship contribute to negative outcomes. Aspergillus, Candida, Cryptococcus, and Pneumocystis are the most common pathogens associated with fatal fungal diseases. These species are responsible for 90% of reported invasive fungal deaths globally. Fungal species employ a diverse and effective array of virulence factors to sabotage, evade, and manipulate host immune systems, allowing for colonisation and dissemination in vivo. Invasive fungal infections are clinically challenging, as they penetrate organs and deep tissues, contributing to the aetiology of respiratory tract, endocarditis, meningitis, and medical device infections and resulting in false negative diagnostic attempts. The 2025 WHO report outlines a lack of diagnostic and therapeutic options available, especially in low-to-middle-income countries. Geographical and economic factors impact fungal disease and mortality rates. There is an urgent need for new approaches to combat fungal diseases clinically with improved biocompatibility profiles. This timely review discusses the prevalent invasive fungal species, namely, Candida, Aspergillus, Cryptococcus, and Pneumocystis, which have high mortality rates, as identified by the WHO priority pathogen list, and discusses recent advances in the treatment of fungal diseases. This dissemination of information is an important aspect of the United Nations Sustainable Development Goals (SDGs) and One Health. Full article

Background: Early diagnosis of Invasive Pulmonary Aspergillosis (IPA) in non-neutropenic ICU patients remains challenging due to the low specificity of radiological findings and the limited reliability of individual biomarkers. This diagnostic uncertainty often delays antifungal treatment and contributes to the high mortality associated with IPA. We aimed to develop a clinically interpretable model for early bedside risk stratification. Methods: We conducted a retrospective study including 298 ICU patients. A Logistic LASSO regression approach was used to identify the most informative predictors of IPA and to develop a parsimonious predictive model. Model performance was assessed through internal exploration and robustness testing under noise perturbation. Results: Three routinely available clinical variables were retained in the final model: pulmonary galactomannan, non-specific pulmonary infiltrates, and patient age, reflecting fungal burden, lung involvement, and host vulnerability, respectively, and identifying patients with a higher probability of culture-positive Aspergillus detection within a clinical context compatible with IPA. The final model showed promising discriminative performance, with an AUC of 0.836 ± 0.075, sensitivity of 0.72, and specificity of 0.74. Despite relying on only three routinely available clinical variables, the model maintained stable performance during internal exploration and robustness analyses. Conclusions: Within this cohort, the combination of positive pulmonary galactomannan, radiological infiltrates, and advanced age identifies a subgroup of ICU patients with a higher probability of microbiological positivity and clinical suspicion of IPA, supporting early risk assessment rather than definitive diagnosis. This simple and transparent predictive model may support early clinical evaluation and risk stratification of ICU patients and assist clinicians in identifying patients requiring further diagnostic assessment. Full article

Chinese chive (Allium tuberosum) suffers severe yield and quality losses from white leaf spot disease caused by Alternaria alternata. Spray-induced gene silencing (SIGS) presents a sustainable alternative to traditional chemical fungicides. To maximize the biocontrol efficacy of this approach, we designed dsRNAs targeting two candidate virulence-associated genes of Alternaria alternata: AaGH10, encoding a cell wall-degrading enzyme critical for host penetration, and AaSOD, an antioxidant enzyme crucial for reactive oxygen species (ROS) scavenging. We comprehensively evaluated the antifungal efficacy by assessing mycelial growth inhibition, spore germination, and lesion development through in vitro and in vivo assays. The results demonstrated that both single and combinatorial treatments effectively inhibited fungal growth and spore germination, thereby reducing disease incidence on detached leaves and intact greenhouse plants. The application of the dual-target dsRNA formulation achieved an 86.7% control efficacy on detached leaves. Furthermore, it significantly alleviated in vivo disease severity, decreasing the average number of necrotic lesions from 15.6 to 1.3 per leaf. These results demonstrate that the dual-target combination exerts an enhanced protective effect compared with individual interventions. This specific dual-target dsRNA formulation establishes a robust foundation for the control of Chinese chive white leaf spot disease. Full article

Background/Objectives: Infectious keratitis and eye injuries, despite being well-recognized ophthalmological diseases, continue to pose diagnostic and therapeutic challenges in clinical practice; therefore, this study was conducted to assess the salient features of care provided by Spanish ophthalmologists working in emergency and ocular surface consultations to patients presenting with keratitis and ocular trauma. Methods: Nationwide cross-sectional survey with the participation of 100 ophthalmologists, including 50 ophthalmologists in emergency care and 50 ocular surface specialists. The study questionnaire assessed diagnostic approaches, treatment strategies, and factors influencing therapeutic decision making. Results: The mean age of participants (51% women) was 37.9 years, with 10.2 years of professional activity. External eye examination, slit lamp examination, fluorescein staining, computed tomography (CT) in penetrating injuries, and microbiological cultures in corneal ulcers were rated as important diagnostic methods. Topical antibiotics were especially recommended for keratitis in general (mean 80.6%) and for contact lens-related keratitis (85.6%). The use of antiseptics was limited. Topical corticosteroids were most commonly selected for viral keratitis with stromal and endothelial involvement (between 24.3% and 50.4%); chlorhexidine (52.0%) and propamidine (26.8%) for Acanthamoeba keratitis; re-epithelizing compounds (20.4%) and artificial tears (29.1%) for actinic keratitis; and topical antifungals for fungal keratitis (77%). Conclusions: This study highlights a limited availability of some specific diagnostic methods and an extensive use of topical antibiotics in the management of keratitis and ocular surface injuries, with relatively limited use of antiseptics. Areas of improvement in therapeutic approach would be awareness of a potential overuse of topical antibiotics with the consequences of increase in antimicrobial resistance. Full article

Vulvovaginal candidiasis (VVC) is one of the most common superficial fungal infections affecting women. A particularly challenging issue is the treatment of recurrent vulvovaginal candidiasis (RVVC)—defined as ≥4 episodes of VVC within 12 months—which affects 5–8% of women with VVC. The development of VVC is influenced by many risk factors related to the host organism and behaviour, including disturbances in the vaginal microflora, hormonal fluctuations, diabetes, hygiene and sexual behaviour. Although C. albicans remains the primary species causing this infection, infections caused by other species, such as Nakaseomyces glabratus and Pichia kudriavzevii, are becoming increasingly common, partly due to the widespread use of azole antifungal drugs and growing drug resistance. Therefore, this publication focuses on a review of the newest literature concerning the epidemiology, diagnosis, current approaches to antifungal susceptibility testing and treatment according to global guidelines. According to the literature, precise species identification and drug susceptibility testing are crucial to avoid therapeutic errors and drug resistance. Moreover, new antifungal drugs such as tetrazoles (oteseconazole) and triterpenoids (ibrexafungerp) are entering clinical practice, offering high efficacy against resistant strains. Probiotics used as adjuvant therapy help restore the homeostasis of the vaginal microbiome; however, due to inconsistent evidence, they are currently not included in treatment recommendations. Full article

Background/Objectives: The clinical impact of empirical antifungal therapy in patients with secondary peritonitis and sepsis remains incompletely established. This study aimed to identify risk factors for fungal infection in this population and the impact of empirical antifungal therapy on clinical outcomes. Methods: This was a retrospective cohort study of critically ill patients who underwent abdominal surgery for visceral lesions. Demographic and microbiological data were extracted from electronic health records. Results: A total of 411 patients, 56.9% male and with an average age of 68.8 ± 15.8 years, admitted following urgent gastrointestinal surgery were included. Fungi were isolated from peritoneal fluid or blood in 13.9% of patients during their ICU stay, with a median hospital length of stay until identification of 10 days (interquartile range 1–19 days). Candida albicans was isolated in 63.2% of the positive samples. Empirical antifungal was provided in 27.3% (n = 112). Each additional surgical procedure (OR: 1.47; p < 0.001) was the only risk factor identified for fungal infection in multivariate logistic regression. ICU mortality among patients with and without fungal documentation was similar, as was ICU mortality among patients with and without empirical antifungal therapy. Conclusions: The mortality impact of fungal isolation remains uncertain. Our results suggest that routine empirical antifungal therapy should be approached with caution, prioritizing targeted therapy for patients with confirmed positive cultures or a persistent, refractory clinical course despite adequate source control. These findings should be interpreted as hypothesis-generating and warrant confirmation in future prospective studies before informing changes in clinical practice. Full article

Fusarium solani is a major soil-borne pathogen responsible for root rot diseases, posing a significant threat to agricultural productivity. The development of environmentally sustainable alternatives to chemical fungicides is therefore urgently needed. This study evaluated the antifungal activity of fermentation broths and extracellular metabolites derived from Tilletia laevis fungi at different developmental stages against F. solani under in vitro conditions. Six test agents, including carbendazim (one positive fungicide control), caffeic acid, phenylacetylglycine, and 6-hydroxypyridine-2-carboxylic acid (candidate bioactive metabolites), were evaluated for mycelial growth inhibition, EC₅₀ values, and physiological responses. All treatments exhibited concentration-dependent inhibitory effects, with carbendazim showing the highest activity (EC₅₀ = 21.26 mg L⁻¹). Among the metabolites, 6-hydroxypyridine-2-carboxylic acid and phenylacetylglycine demonstrated notable antifungal efficacy, particularly at higher concentrations. Fermentation broths from the promycelial stage showed stronger inhibition than those from the teliospore stage, indicating stage-specific metabolite activity. Biochemical analyses of F. solani mycelia revealed significant changes in soluble protein, soluble sugar, and antioxidant enzyme activities (SOD and POD), suggesting that antifungal effects are mediated through metabolic disruption and oxidative stress. These findings highlight the potential of T. laevis-derived metabolites as eco-friendly biofungicides and provide a theoretical basis for sustainable management of soil-borne diseases. Further studies are required to identify active compounds and validate their efficacy under field conditions. Full article

Yeast infections are becoming an increasing public health concern, mainly due to the spread of opportunistic species and the emergence of strains resistant to commonly used antifungal drugs. Marine resources are a promising source of bioactive compounds, including polysaccharides and other biopolymers with potential antifungal applications. In this study, a sulphated polysaccharide-rich extract was obtained from the red alga Jania pedunculata var. adhaerens and chemically characterized. Its antifungal activity was compared with that of a commercial chitosan formulation against clinically relevant yeasts, including species of Candida, Cryptococcus, Clavispora, Naganishia and Trichosporon. Growth kinetics were monitored in liquid medium over 24 h, and antifungal activity was evaluated through growth rate analysis, growth inhibition at 20 h and susceptibility clustering. The sulphated polysaccharide-rich extract showed moderate but consistent growth inhibition, with the strongest effects observed at 5 mg mL⁻¹. Maximum growth inhibition reached 60.9% in Cryptococcus deuterogattii and 59.8% in Candida albicans, although no complete inhibition was observed within the tested concentration range. Chitosan showed a stronger antifungal effect, with minimal inhibitory concentration (MIC) values between 10 and 20 µg mL⁻¹ in several species and maximum inhibition values above 80% in the most susceptible yeasts. However, C. albicans showed marked resistance to chitosan, with inhibition below 12%. K-means clustering confirmed distinct susceptibility profiles between treatments, supporting a species-dependent response. Overall, these results highlight marine-derived biopolymers as promising antifungal candidates and show that chitosan and algal sulphated polysaccharides produce distinct, species-dependent antifungal profiles. Full article

Banana is a typical climacteric fruit that rapidly undergoes ripening, peel browning, softening, moisture loss, and fungal decay during postharvest storage, leading to severe quality deterioration and a shortened shelf life. In this study, a sodium alginate (SA)-based edible coating enriched with Isodon serra extract (IE) and Plinia cauliflora (jaboticaba) leaf extract (JE) was developed and evaluated for its antioxidant, antifungal, and preservation effects on banana fruit. The two extracts exhibited distinct functional properties: IE showed strong inhibitory activity against Colletotrichum musae, whereas JE displayed superior radical scavenging capacity. When incorporated into the coating system, this functional complementarity translated into improved preservation performance. The composite coating (SA-IE-JE) effectively suppressed anthracnose development, reduced peel browning, and delayed ripening progression, as evidenced by an 11.8% reduction in fruit weight loss (11.48% vs. 13.01%), an 11.6% decrease in MDA accumulation (89.96 vs. 101.75), a 51.3% reduction in PPO activity (526 U/g vs. 1080 U/g), sustained TPC, and a slower increase in total soluble solids after 5 days of storage. All coating treatments improved postharvest quality compared with the uncoated control, while SA-IE and SA-IE-JE generally showed stronger preservation effects than SA alone. In particular, SA-IE-JE was more effective in reducing peel browning, delaying the increase in PPO activity, and suppressing anthracnose lesion expansion. These findings highlight that SA coating supplemented with IE and JE can serve as a promising, environmentally friendly strategy for maintaining banana quality and reducing postharvest disease. Our study provides a potential basis for the development of plant-extract-enriched edible coatings for banana preservation. Full article

Sclerotinia sclerotiorum causes destructive sclerotinia stem rot and severe yield losses in global rapeseed production. The Bacillus biocontrol strain YZUS007 serves as an eco-friendly alternative to synthetic fungicides, yet its control efficacy fluctuates under complex field conditions. This study aimed to investigate whether low-dose ZnO NPs could enhance the biocontrol efficacy of YZUS007 and to elucidate the underlying mechanisms. We isolated and identified the antagonistic strain Bacillus siamensis YZUS007 from the rhizosphere soil of healthy Brassica napus, which exhibited an in vitro pathogen inhibition rate of 78.4 ± 0.7%. Pot tests showed that YZUS007 (BC) achieved 60.79% control efficacy, whereas the YZUS007 + 20 μg/mL ZnO NPs group (BZ) reached 74.68%. Cell-free filtrate of YZUS007 (EC) had a 50.44% control efficacy, and filtrate with ZnO NPs (EZ) increased efficacy to 58.08%. LC-MS/MS identified four extracellular metabolites with increased relative abundances: cinnamic acid, sesamol, patchouli alcohol and 2-phenylbutyric acid. The combined treatment boosted defense enzyme activities and induced higher expression of the defense-related genes RBOH, PR1 and WRKY33. Collectively, low-concentration ZnO NPs significantly enhanced the biocontrol performance of YZUS007 by promoting antifungal metabolite accumulation, providing a low-dose, nanomaterial-assisted strategy for sustainable sclerotinia rot management. Full article