Search Results (908)

Botrytis cinerea is a highly versatile pathogenic fungus, causing significant damage across a wide range of plant species. A central focus of this review is the recent advances made through proteomics, an advanced molecular tool, in understanding the mechanisms of B. cinerea infection. Recent advances in mass spectrometry-based proteomics—including LC-MS/MS, iTRAQ, MALDI-TOF, and surface shaving—have enabled the in-depth characterization of B. cinerea subproteomes such as the secretome, surfactome, phosphoproteome, and extracellular vesicles, revealing condition-specific pathogenic mechanisms. Notably, in under a decade, the proportion of predicted proteins experimentally identified has increased from 10% to 52%, reflecting the rapid progress in proteomic capabilities. We explore how proteomic studies have significantly enhanced our knowledge of the fungus secretome and the role of extracellular vesicles (EVs), which play key roles in pathogenesis, by identifying secreted proteins—such as pH-responsive elements—that may serve as biomarkers and therapeutic targets. These technologies have also uncovered fine regulatory mechanisms across multiple levels of the fungal proteome, including post-translational modifications (PTMs), the phosphomembranome, and the surfactome, providing a more integrated view of its infection strategy. Moreover, proteomic approaches have contributed to a better understanding of host–pathogen interactions, including aspects of the plant’s defensive responses. Furthermore, this review discusses how proteomic data have helped to identify metabolic pathways affected by novel, more environmentally friendly antifungal compounds. A further update on the advances achieved in the field of proteomics discovery for the organism under consideration is provided in this paper, along with a perspective on emerging tools and future developments expected to accelerate research and improve targeted intervention strategies. Full article

The secondary metabolites of the fungus Penicillium thymicola, fumiquinazolines F and G, have antibacterial and antifungal characteristics; however, their potential anti-tumor action against human cancer cells remains unknown. The goal of our study was to determine the biological efficacy of fumiquinazolines F and G on breast and prostate cancer cells. Cancer cell proliferation and migration were monitored in real time using xCELLigence technology and flow cytometry. Alterations in mRNA and protein expression were assessed by RT-qPCR, ELISA, and Western blotting. Our data indicate that fumiquinazolines F and G are more effective in inhibiting breast cancer cell proliferation than prostate cancer cells. Fumiquinazoline F is active against both hormone-dependent epithelial MCF-7 (IC₅₀ 48 μM) and hormone-resistant triple-negative mesenchymal MDA-MB-231 breast cancer cells (IC₅₀ 54.1 μM). The metabolite has low cytotoxicity but slows cell cycle progression. In fumiquinazoline F-treated MDA-MB-231 cells, the levels of proteins implicated in epithelial–mesenchymal transition (EMT) (such as E-cadherin, vimentin, and CD44) fluctuate, resulting in a decrease in cell migratory rate and adhesion to a hyaluronic acid-coated substrate. Thus, fumiquinazolines F and G exhibit anticancer activity by inhibiting EMT, cell proliferation, and migration, hence reverting malignant cells to a less pathogenic phenotype. The compound’s multi-target anticancer profile underscores its potential for further exploration of novel EMT-regulating pathways. Full article

Common bean (Phaseolus vulgaris L.) is a critical protein-rich legume supporting food and nutritional security globally. However, Fusarium wilt, caused by Fusarium solani, remains a major constraint to production, with yield losses reaching up to 84%. While biocontrol strategies have been explored, most microbial agents are sourced from mesophilic environments and show limited effectiveness under abiotic stress. Here, we report the isolation and characterization of extremophilic Bacillus spp. from the hypersaline Lake Bogoria, Kenya, and their biocontrol potential against F. solani. From 30 isolates obtained via serial dilution, 9 exhibited antagonistic activity in vitro, with mycelial inhibition ranging from 1.07–1.93 cm 16S rRNA sequencing revealed taxonomic diversity within the Bacillus genus, including unique extremotolerant strains. Molecular screening identified genes associated with the biosynthesis of antifungal metabolites such as 2,4-diacetylphloroglucinol, pyrrolnitrin, and hydrogen cyanide. Enzyme assays confirmed substantial production of chitinase (1.33–3160 U/mL) and chitosanase (10.62–28.33 mm), supporting a cell wall-targeted antagonism mechanism. In planta assays with the lead isolate (B7) significantly reduced disease incidence (8–35%) and wilt severity (1–5 affected plants), while enhancing root colonization under pathogen pressure. These findings demonstrate that extremophile-derived Bacillus spp. possess robust antifungal traits and highlight their potential as climate-resilient biocontrol agents for sustainable bean production in arid and semi-arid agroecosystems. Full article

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of “One Health” strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy. Full article

The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the target-specific binding efficacy of insect-derived antifungal peptides (n = 37) as possible alternatives to traditional antifungal treatments. Using computational methods, namely the HPEPDOCK and HDOCK platforms, molecular docking was performed to evaluate the interactions between selected key fungal targets, lanosterol 14-demethylase, or LDM (PDB ID: 5V5Z), secreted aspartic proteinase-5, or Sap-5 (PDB ID: 2QZX), N-myristoyl transferase, or NMT (PDB ID: 1NMT), and dihydrofolate reductase, or DHFR, of C. albicans. The three-dimensional peptide structure was modelled through the PEP-FOLD 3.5 tool. Further, we predicted the physicochemical properties of these peptides through the ProtParam and PEPTIDE 2.0 tools to assess their drug-likeness and potential for therapeutic applications. In silico results show that Blap-6 from Blaps rhynchopeter and Gomesin from Acanthoscurria gomesiana have the most antifungal potential against all four targeted proteins in Candida sp. Additionally, a molecular dynamics simulation study of LDM-Blap-6 was carried out at 100 nanoseconds. The overall predictions showed that both have strong binding abilities and are good candidates for drug development. In in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. C. tropicalis demonstrated relative resistance to complete eradication by both peptides. The present study provides evidence to support the antifungal activity of certain insect peptides, with potential to be used as alternative drugs or as a template for a new synthetic or modified peptide in pursuit of effective therapies against Candida spp. Full article

Candidozyma auris is a multidrug-resistant, thermo- and osmotolerant yeast capable of persisting on biotic and abiotic surfaces, attributes likely linked to its cell wall composition. Here, seven putative genes encoding yapsins, aspartyl proteases GPI-anchored to the membrane or cell wall, were identified in the genomes of C. auris CJ97 and 20-1498, from clades III and IV, respectively. The C. auris YPS1 gene is orthologous to the SAP9 of C. albicans. The YPS7 gene is orthologous to YPS7 in C. glabrata and S. cerevisiae, so that they may share similar roles. An in silico analysis suggested an interaction between pepstatin and the catalytic domain of Yps1 and Yps7. Although this inhibitor, when combined with caffeine, had a subtle effect on the growth of C. auris, it induced alterations in the cell wall. CauYPS1 and CauYPS7 expression increased under nutrient starvation and NaCl, and at 42 °C. The transcriptome of the 20-1498 strain suggests that autophagy may play a role in thermal stress, probably degrading deleterious proteins or maintaining cell wall and vacuolar homeostasis. Therefore, CauYps1 and CauYps7 may play a role in the cell wall integrity of C. auris in stress conditions, and they could be a target of new antifungal or antivirulence agents. Full article

Candida albicans is a clinically important fungal pathogen capable of causing both superficial and systemic infections, particularly in immunocompromised individuals. A key factor contributing to its pathogenicity is its ability to form biofilms, structured microbial communities that confer significant resistance to conventional antifungal therapies. Addressing this challenge, we explored the antivirulence potential of acridine derivatives, a class of heterocyclic aromatic compounds known for their diverse biological activities, including antimicrobial, antitumor, and antiparasitic properties. In this study, a series of acridine derivatives was screened against C. albicans biofilms, revealing notable inhibitory activity and highlighting their potential as scaffolds for the development of novel antifungal agents. Among the tested compounds, acridine-4-carboxylic acid demonstrated the most promising activity, significantly inhibiting the biofilm formation at 10 µg/mL without affecting planktonic cell growth, and with a minimum inhibitory concentration (MIC) of 60 µg/mL. Furthermore, it attenuated filamentation and cell aggregation in a fluconazole-resistant C. albicans strain. Toxicity assessments using Caenorhabditis elegans and plant models supported its low-toxicity profile. These findings highlight the potential of acridine-based scaffolds, particularly acridine-4-carboxylic acid, as lead structures for the development of therapeutics targeting both fungal growth and biofilm formation in Candida albicans infections. Full article

Satureja montana (SM) is acknowledged as a highly pharmacologically important species within the vast Lamiaceae family, indigenous to the Balkan area. Traditionally, this plant has been employed as a culinary spice, especially in Bulgarian gastronomy. Additionally, it is widely recognized that mental health is affected by the nature and quality of dietary consumption. Results: Ethnopharmacological research underscores the potential of SM in influencing various chronic ailments, including depression and anxiety. This plant is distinguished by a rich variety of secondary metabolites that display a broad spectrum of biological activities, such as antioxidant, antidiabetic, anti-inflammatory, analgesic, antibacterial, antiviral, and antifungal effects. Particularly, two of its active phenolic compounds, rosmarinic acid and carvacrol, reveal notable anxiolytic and antidepressive properties. This review aims to explore the capacity of SM to improve mental health through its plentiful phenolic components. Recent studies indicate their efficacy in addressing Alzheimer’s-type dementia. A notable correlation exists among depression, anxiety, and cognitive decline, which includes dementia. Considering that Alzheimer’s disease (AD) is a multifaceted condition, it requires multi-targeted therapeutic strategies for both prevention and management. Conclusions: Satureja montana is recognized as potential candidate for both the prevention and management of various mental health disorders, including dementia. Full article

Cryptococcus neoformans is an opportunistic fungal pathogen and causative agent of cryptococcosis and cryptococcal meningitis (CM). Cryptococcal disease accounts for up to 19% of AIDS-related mortalities globally, warranting its label as a pathogen of critical priority by the World Health Organization. Standard treatments for CM rely heavily on high doses of antifungal agents for long periods of time, contributing to the growing issue of antifungal resistance. Moreover, mortality rates for CM are still incredibly high (13–78%). Attempts to create new and effective treatments have been slow due to the complex and diverse set of immune-evasive and survival-enhancing virulence factors that C. neoformans employs. To bolster the development of better clinical tools, deeper study into host–Cryptococcus proteomes is needed to identify clinically relevant proteins, pathways, antigens, and beneficial host response mechanisms. Mass spectrometry-based proteomics approaches serve as invaluable tools for investigating these complex questions. Here, we discuss some of the insights into cryptococcal disease and biology learned using proteomics, including target proteins and pathways regulating Cryptococcus virulence factors, metabolism, and host defense responses. By utilizing proteomics to probe deeper into these protein interaction networks, new clinical tools for detecting, diagnosing, and treating C. neoformans can be developed. Full article

Zeolites, microporous aluminosilicates with tuneable physicochemical properties, have garnered increasing attention in dermatology due to their antimicrobial, detoxifying, and drug delivery capabilities. This review evaluates the structural characteristics, therapeutic mechanisms, and clinical applications of zeolites—including clinoptilolite, ZSM-5, ZIF-8, and silver/zinc-functionalized forms—across skin infections, wound healing, acne management, and cosmetic dermatology. Zeolites demonstrated broad-spectrum antibacterial and antifungal efficacy, enhanced antioxidant activity, and biocompatible drug delivery in various dermatological models. Formulations such as silver–sulfadiazine–zeolite composites, Zn–clinoptilolite for acne, and zeolite-integrated microneedles offer innovative avenues for targeted therapy. Zeolite-based systems represent a promising shift toward multifunctional, localized dermatologic treatments. However, further research into long-term safety, formulation optimization, and clinical validation is essential to transition these materials into mainstream therapeutic use. Full article

Essential oils (EOs) are widely recognized for their antifungal properties, but their efficacy against specific phytopathogenic fungi associated with banana (Musa paradisiaca) rot remains underexplored. This study aimed to evaluate the antifungal potential of EOs from Origanum vulgare, Salvia rosmarinus, Syzygium aromaticum, Thymus vulgaris, Cinnamomum verum, and Ocimum basilicum against five fungal species isolated from infected banana peels. Fungal isolates were obtained using PDA medium supplemented with chloramphenicol and were purified by weekly subculturing. Morphological and microscopic characterization was complemented by molecular identification based on ITS sequencing and phylogenetic reconstruction using Neighbor-Joining and UPGMA methods in MEGA v11. In vitro and ex vivo antifungal assays were performed at EO concentrations ranging from 200 to 1000 ppm. Thyme oil exhibited the strongest inhibitory effect, with complete growth suppression at 1000 ppm. Cinnamon and oregano also demonstrated effective inhibition at 600 ppm, while clove, rosemary, and basil were markedly less effective. Statistical analysis confirmed significant effects of EO type and concentration on fungal growth (p < 0.001). Molecular results showed strong phylogenetic support for isolate identification, with bootstrap values above 93% in most clades. These findings support the selective use of specific EOs as sustainable alternatives to synthetic fungicides in the postharvest management of banana diseases and provide a molecularly supported basis for their targeted application in integrated control strategies. Full article

In the present research, metal–organic framework-5 (MOF-5) was synthesized and loaded with zerumbone (ZER@MOF-5), followed by the evaluation of its anticancer, antibacterial, antifungal, DNA-binding, and free radical scavenging potentials. The synthesized nanoparticles were characterized using X-ray diffraction, ultraviolet–visible spectroscopy, Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. The in vitro anticancer activity of ZER@MOF-5 was studied in a human breast cancer cell line (MCF-7) using the CCK-8 assay. The interaction of ZER@MOF-5 with pBR322 plasmid DNA was assessed by gel electrophoresis. The antimicrobial effect of ZER@MOF-5 was examined in gram-positive and gram-negative bacterial strains and yeast strains using the microdilution method. The free radical scavenging activity was assessed using the DPPH assay. Cytotoxicity assay revealed a notable enhancement in the anticancer activity of zerumbone upon its encapsulation into MOF-5. The IC₅₀ value for ZER@MOF-5 was found to be 57.33 µg/mL, which was lower than that of free zerumbone (IC₅₀: 89.58 µg/mL). The results of the DNA-binding experiment indicate that ZER@MOF-5 can bind to target DNA and cause a conformational change in DNA. The results of the antibacterial activity experiment showed that the antibacterial ability of ZER@MOF-5 was limited compared to free zerumbone. The results of the DPPH assay demonstrated that the antioxidant activity of free zerumbone was higher than that of ZER@MOF-5. MOFs encapsulate compounds within their porous crystalline structure, which leads to prolonged circulation time compared to single ligands. Although the unique structure of MOFs may limit their antibacterial and antioxidant activity in the short term, it may increase therapeutic efficacy in the long term. However, to fully understand the long-term antibacterial and antioxidant effects of the ZER@MOF-5, further comprehensive in vitro and in vivo experiments are necessary. This finding indicates that the MOF-5 could potentially be an impressive carrier for the oral administration of zerumbone. Full article

Biocontrol is one of the most promising alternatives to chemical preservatives for food preservation. This study investigated the biocontrol potential of yeasts isolated from raw milk cheese against spoilage moulds. Eighty-four native yeast strains were screened for antagonistic activity against Penicillium commune, Fusarium verticillioides, and Mucor plumbeus/racemosus via confrontation using a milk-based culture medium. Fifteen strains from the species Pichia jadinii, Kluyveromyces lactis, Kluyveromyces marxianus, and Geotrichum candidum exhibited significant antagonistic activity (inhibition zone > 2 mm) against M. plumbeus/racemosus and F. verticillioides. The modelling of the impact of ripening conditions revealed that temperature was the primary factor influencing yeast antagonism. In addition, notable variability at both species and strain levels was found. The antagonist activity was associated with different mechanisms depending on the species and strains. K. lactis stood out for its proteolytic activity and competition for iron and manganese. Additionally, two strains of this species (KL890 and KL904) were found to produce volatile organic compounds with antifungal properties (phenylethyl alcohol and 1-butanol-3-methyl propionate). G. candidum GC663 exhibited strong competition for space, as well as the ability to parasitise hyphae linked to its pectinase and β-glucanase activity. The latter enzymatic activity was detected in all P. jadinii strains, with P. jadinii PJ433 standing out due to its proteolytic activity. In a cheese matrix, the efficacy of eight yeast strains against three target moulds was assessed, highlighting the potential of G. candidum GC663 and P. jadinii PJ433 as biocontrol agents, exhibiting high and moderate efficacy, respectively, in controlling the growth of F. verticillioides and M. plumbeus/racemosus. Nonetheless, further research is necessary to elucidate their full spectrum of antifungal mechanisms and to validate their performance under industrial-scale conditions, including their impact on cheese quality. Full article

Dendrimers, 4-dimethylamino-1,8-naphthalimide (DAB) and its halogenated analog 3-bromo-4-dimethylamino-1,8-naphthalimide (DAB-Br), were evaluated on eukaryotic cells, human HFF-1 fibroblast cells, and five fungal species. Although both dendrimers have demonstrated antibacterial and antiviral potential, thus far, their effects on eukaryotic cells, particularly human and fungal cells, have not been investigated. For this purpose, their cytotoxicity, mechanisms of cellular entry, and antifungal activity were studied. Dynamic light scattering measurements revealed that both dendrimers exhibited positive surface charges (+28 to +35 mV), good colloidal stability, and nanoscale dimensions (117–234 nm), facilitating interactions with target cells. The MTT assay showed that DAB was more cytotoxic toward HFF-1 cells (IC₅₀ = 27 µg/mL) compared to DAB-Br (IC₅₀ = 68 µg/mL). In contrast, the resazurin-based antifungal assay demonstrated that DAB-Br had superior antifungal activity, achieving a lower minimum inhibitory concentration (0.148 µg/µL), compared to DAB (0.295 µg/µL). A trypan blue exclusion test revealed that both dendrimers entered cells through membrane permeabilization, either temporarily or permanently, depending on the concentration and exposure time. At concentrations above 30 µg/mL, irreversible permeabilization was observed within two hours of treatment, accompanied by a decrease in membrane lipid order, indicating altered membrane integrity and permeability. Conversely, at lower concentrations (7.5–15 µg/mL), dendrimers induced only temporary membrane permeabilization, with membranes remaining intact, suggesting a reversible interaction with the lipid bilayer. Conducting thorough and systematic research to fully explore their biological activities could provide valuable insight for future applications. Full article

Fungal melanin plays a vital role in the survival, reproduction, infection, and environmental adaptation of plant pathogenic fungi. To develop innovative strategies for managing plant fungal diseases, comprehensive investigations into melanin are imperative. Such research is fundamental to elucidating the mechanistic basis of fungal pathogenesis and holds promise for the design of targeted interventions against melanin-mediated virulence determinants. This review systematically elaborates on the classification of fungal melanin in plant pathogens, provides a detailed analysis of the biosynthetic processes of 3,4-dihydroxyphenylalanine (DOPA) and 1,8-dihydroxynaphthalene melanin (DHN melanins), and reveals the catalytic functions and regulatory mechanisms of key enzymes within these pathways. Melanin modulates fungal virulence by influencing appressorial integrity and turgor pressure formation, thereby participating in the host infection process and the formation of overwintering sclerotia. Melanin provides stress resistance by protecting against extreme environmental factors, including UV radiation and high temperatures. It also has the capacity to absorb heavy metals, which increases pathogen survival under adverse conditions. Furthermore, the review also explores the mechanisms of action of melanin inhibitors that target plant pathogenic fungi, providing a theoretical foundation for developing efficient and environmentally friendly antifungal medications. The complex biosynthesis pathways and diverse biological functions of fungal melanin highlight its significant theoretical and practical importance for elucidating pathogenic mechanisms and formulating scientific control strategies. Full article