Antifungal mechanisms of 4-hydroxy-5-methyl-3(2H)-furanone against Botrytis cinerea and its application in postharvest crabapples.

Fungal infections pose a major worldwide health risk, as newly emerging pathogens and the increasing spread of drug resistance are now severely challenging current therapeutic and diagnostic tools. Candidozyma auris embodies both of these aspects as it is an urgent threat that is resistant to several antifungal classes. The lack of effective drugs is driving the development of innovative strategies, among them monoclonal antibodies. This study investigates the in vivo and ex vivo safety and efficacy of the humanized monoclonal antibody Dia-T51, administered alone or in combination with amphotericin B (AMB), in Galleria mellonella model. Against C. auris infection, Dia-T51 demonstrated good therapeutic efficacy and provided near-complete protection when used prophylactically. The synergy between Dia-T51 and AMB observed in vitro was confirmed in vivo, resulting in enhanced larval survival and a significant reduction in fungal burden. The results strengthen the profile of Dia-T51 as a promising biological agent against fungal infections both for its standalone potential (via direct inhibition and immune-mediated mechanisms) and for its ability to amplify the efficacy of conventional antifungals.

Nonanoic acid-containing polymethyl methacrylate denture base inhibits Candida albicans growth and biofilm formation.

Candidiasis, caused by yeasts of the Candida genus, is increasingly characterized by a high prevalence of clinical isolates resistant to conventional antifungals, rendering the development of novel therapeutic strategies paramount. Drug repurposing has emerged as a key strategy, utilizing established pharmaceuticals for indications beyond their original design; notably, haloperidol (HAL) has shown promising antimicrobial potential. In this context, the present study evaluates the activity of haloperidol, both as a monotherapy and in combination with conventional antifungals, against fluconazole-susceptible and fluconazole-resistant Candida spp. clinical strains. Furthermore, we investigate the underlying mechanisms of its antifungal action. Experimental approaches included broth microdilution assays to determine the Minimum Inhibitory Concentration (MIC), checkerboard assays for synergistic analysis, and cellular assessments via flow cytometry and fluorescence microscopy. Haloperidol displayed MIC values between 26.67 and 256 μg/mL. Synergistic interactions were identified between haloperidol and the azoles fluconazole and itraconazole, alongside a 2.5 % synergy rate with amphotericin B. Additionally, mechanistic assays confirmed that haloperidol induces programmed cell death (apoptosis) in C. albicans and C. auris strains. The oxidative stress caused by haloperidol altered Ca2+ homeostasis, followed by mitochondrial membrane depolarization, reduced ATP production, cytochrome c release into the cytosol and metacaspase activation, reduced viability, phosphatidylserine externalization, promoted fragmentation, damage and methylation of DNA. It also induced expression of genes related to oxidative stress. It reduced mitochondrial depolarization and decreased the reduction of glutathione (GSH), causing morphological alterations. The results suggest the apoptotic pathway as the main antifungal mechanism of haloperidol.

Background:Candida albicans is the most clinically significant opportunistic fungal pathogen, and the growing resistance to conventional antifungals, particularly azoles and echinocandins, highlights the urgent need for alternative therapeutic strategies. Although lactic acid bacteria (LAB) have shown inhibitory potential against C. albicans, the relative contributions of live probiotics, heat-inactivated postbiotics, and cell-free supernatants (CFSs) have rarely been compared in parallel under physiologically relevant conditions against a clinical oral isolate. Results: This study systematically evaluated the antifungal activity of Lactiplantibacillus plantarum 299V, Lactobacillus delbrueckii subsp. bulgaricus ATCC 11842, and Lactobacillus acidophilus ATCC 4356 using co-culture assays, minimum inhibitory concentration tests, agar well diffusion assays, and optical microscopy. L. plantarum achieved the strongest inhibitory effect in co-culture, reducing C. albicans viability by 2.39 log10 CFU/mL after 24 h, correlating with the greatest acidification of the culture medium. Methods: CFS from L. acidophilus inhibited fungal growth by 79.01% at native pH, declining to 28.35% upon neutralization to pH 7, confirming that antifungal efficacy is largely pH-dependent and driven by undissociated organic acids. At probiotic concentrations of 1 × 109 CFU/mL, all strains completely suppressed fungal growth. Heat-inactivated postbiotics exhibited up to 95.14% inhibition in MIC assays; however, microscopic analysis revealed coaggregation between postbiotic and fungal cells, which likely interfered with optical density measurements. Conclusions: These findings establish that LAB-mediated antifungal activity is multifactorial and assay-dependent, and highlight the importance of distinguishing between probiotic, postbiotic, and CFS effects when developing LAB-based antifungal strategies.

Lomentospora prolificans and Scedosporium spp. are emerging non-Aspergillus moulds causing invasive fungal disease (IFD) in onco-haematology patients. Rhino-sino-orbital and/or central nervous system (CNS) infections are poorly described yet associated with high mortality. We aimed to characterize clinical, microbiological, treatment, and outcome features of rhino-sino-orbital and/or CNS infections due to these moulds in an onco-haematology population. We retrospectively reviewed proven/probable IFD patients with rhino-sino-orbital and/or CNS involvement from 2010 to 2024 caused by L. prolificans and Scedosporium spp. at two Australian tertiary centres in adults with cancer. Eighteen episodes were analysed; 94.5% had haematological malignancy, mainly acute myeloid leukaemia (41.5%), and 53% were haematopoietic stem cell transplant recipients. Lomentospora prolificans predominated (83%) and displayed intrinsic resistance to conventional antifungals. Olorofim showed potent in vitro activity when tested (n=5, MIC 0.125-0.5mg/l). Disseminated disease occurred in 78%, mainly affecting lung (79%), CNS (64%), and eye (43%). Initial combination therapy with a voriconazole and terbinafine-including regimen was used in 87.5% and surgery in 50%; olorofim was administered to five patients. Overall mortality was high: 56% at 30-day and 67% at 180-day follow-up, with early death noted if there was CNS involvement (70%). Lower 30-day and 180-day mortality was observed in localized rhino-sino-orbital and Scedosporium spp. infections (0% and 20%, respectively), particularly when surgery and olorofim were used. Our results underline the high mortality from L. prolificans infections in onco-haematology patients with disseminated disease or CNS involvement. Early aggressive surgery and novel antifungals may improve outcomes, but prospective multicentre studies are needed to define optimal treatment strategies.

Invasive fungal infections (IFIs), predominantly caused by Candida albicans, are a significant threat to immunocompromised individuals. The emergence of drug-resistant strains has intensified the need for novel antifungal agents. Natural naphthoquinones, including 5,8-dihydroxy-1,4-naphthoquinone (DHNQ, also as PNP-02), have broad-spectrum antimicrobial properties, but their antifungal potential against C. albicans remains underexplored. This study evaluates the antifungal activity of DHNQ derivatives and elucidates their mechanisms of action. The antifungal properties of these compounds were evaluated using the Kirby-Bauer disk diffusion method, broth microdilution assays, and phenotypic screening. DHNQ was identified as the most effective compound, and further investigation focused on its effects on C. albicans growth, biofilm formation, hyphal development, and underlying mechanisms, including oxidative stress induction and mitochondrial dysfunction. In a murine candidiasis model, DHNQ significantly reduced the fungal burden in both the kidneys and the skin, with a minimum inhibitory concentration (MIC) ranging from 2 to 8 μg/mL, exceeding the activity of fluconazole against clinical isolates of fluconazole-resistant C. albicans strains by over 32 times. Mechanistic investigations revealed that DHNQ exerts its antifungal effects through a multi-pronged approach: inhibiting glycolysis, disrupting biofilm and hyphal formation, and inducing oxidative stress-mediated mitochondrial dysfunction. Notably, DHNQ exhibited low cytotoxicity in vitro and no observable toxicity in vivo. These properties make it a promising lead molecule for future optimization and development of treatments for C. albicans infections, pending crucial evaluations of its selectivity and safety in host environments.IMPORTANCEIn summary, this study demonstrated that DHNQ exhibits potent and broad-spectrum antifungal activity, showing significant efficacy against C. albicans both in vitro and in vivo. Unlike conventional antifungals, DHNQ disrupted the virulence of C. albicans by inhibiting glycolysis, suppressing biofilm formation, and inducing oxidative stress-mediated mitochondrial dysfunction. These findings not only highlight the promising potential of DHNQ as a treatment for C. albicans infections but also provide critical insights that may facilitate the development of new antifungal agents.

Opportunistic fungal infections have become an increasing health threat, particularly in immunocompromised individuals, due to their high virulence, biofilm-forming capacity, and resistance to conventional antifungals. Given the limited therapeutic arsenal, drug repurposing represents a promising strategy for antifungal discovery. This study evaluated the antifungal activity and mechanisms of auranofin and iodoquinol against filamentous fungi listed as World Health Organization (WHO) priority pathogens, including Aspergillus fumigatus, Fusarium oxysporum, Scedosporium boydii, Lomentospora prolificans, Rhizopus oryzae, Mucor velutinosus, and Cunninghamella sp. Although Aspergillus flavus is not included in the WHO priority list, it was included in this study due to its clinical relevance as a major cause of aspergillosis and fungal rhinosinusitis. Auranofin displayed fungicidal activity against Aspergillus spp., L. prolificans, S. boydii, and R. oryzae, while iodoquinol exhibited potent but mainly fungistatic effects, with minimum inhibitory concentration values ranging from 0.625 to 20 µM. Both compounds inhibited early growth and reduced preformed biofilms by over 50% in biomass and metabolic activity. Stress susceptibility and fluorescence assays indicated that auranofin interferes with lipid homeostasis, cell wall integrity, and oxidative stress responses, whereas iodoquinol alters membrane lipids, mannose, and chitin distribution, suggesting multitarget surface effects. Scanning electron microscopy revealed consistent ultrastructural alterations, including hyphal deformation and increased extracellular matrix deposition in A. fumigatus and F. oxysporum treated with sub-inhibitory drug concentrations, corroborating the observed cellular stress responses. Drug interaction assays demonstrated additive or synergistic effects with voriconazole and amphotericin B, but not with posaconazole. Overall, auranofin and iodoquinol exhibit broad-spectrum antifungal activity, disrupt fungal morphology and physiology, and represent promising repurposed candidates for developing novel combination therapies against refractory mycoses.IMPORTANCEMycoses caused by opportunistic fungi are an increasingly public health problem, particularly in immunocompromised individuals, due to their high virulence and resistance to conventional antifungals. The World Health Organization's priority fungal pathogens list points out a variety of filamentous fungi, such as Aspergillus fumigatus, A. flavus, Fusarium oxysporum, Scedosporium boydii, Lomentospora prolificans, Rhizopus oryzae, Mucor velutinosus, and Cunninghamella sp. Given the limited therapeutic arsenal to combat them, drug repurposing represents a promising strategy for antifungal discovery. The present study evaluated the antifungal activity and some cellular alterations caused by auranofin and iodoquinol, which are already available in clinical settings to treat rheumatoid arthritis and infections by amoeba, respectively. The data presented in the study revealed that both drugs display a wide spectrum of action against different fungal pathogens, as well as contribute to highlight the potential of them as repurposing drugs to be investigated as alternatives for the treatment of mycoses.

Antimicrobial resistance is a momentous global threat, demanding innovative approaches to combat drug-resistant pathogens. As a prevalent fungal pathogen, Candida albicans exhibits increasing resistance to conventional antifungals, especially the azoles. This study explores a novel approach combining sophorolipids (SLs), a glycolipid biosurfactant, with clinical azoles, including fluconazole (FLZ), itraconazole (ITZ), and ketoconazole (KCZ), against C. albicans biofilms. SLs from the yeast Starmerella riodocensis exhibited promising metabolic reduction and antibiofilm activity against Candida biofilms, with a biofilm inhibitory concentration (BIC50) of 512mg/L. Among the tested azoles, ITZ exhibited the highest antibiofilm efficacy, prompting further investigation of SLs combinations. The ITZ-SLs combination markedly enhanced antibiofilm activity against preformed biofilms, with ITZ and SLs concentrations reduced by 16-fold and 4-fold, respectively, compared with their individual treatments (achieving a BIC₅₀ of 1mg/L ITZ and 128mg/L SLs). Quantitative real-time polymerase chain reaction analysis revealed significant downregulation of essential biofilm-associated genes such as BCR1, EFG1, and CDC28, demonstrating SLs's ability to inhibit various stages of biofilm development and stability. Thus, the synergy observed with azole drugs, particularly ITZ and SLs, was highly effective in biofilm removal, highlighting the compatibility of anti-biofilm biosurfactant SLs with some antifungal agents.

Background: Invasive pulmonary aspergillosis (IPA) remains a lethal infection in immunocompromised hosts, with treatment limited by the poor pharmacokinetics and toxicity of conventional antifungals. Lipid nanoparticles (LNPs) offer a promising delivery platform to overcome these barriers, yet a synthesis of pre-clinical evidence is lacking. Objective: This systematic review aimed to synthesize pre-clinical evidence on the therapeutic potential of LNP-based systems for delivering antifungal agents in the treatment of IPA. Methods: Following PRISMA 2020 guidelines, a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted for studies published from 2014-2024. Included were pre-clinical studies evaluating LNP-encapsulated antifungals in models of IPA, compared to conventional formulations. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using the SYRCLE tool. Results: Eight studies met the inclusion criteria. All reported that LNP formulations (of amphotericin B, voriconazole, itraconazole, or posaconazole) significantly reduced lung fungal burden and/or improved survival compared to free drug controls (p<0.05). LNPs consistently enhanced drug deposition in lung tissue and, for amphotericin B, demonstrated a reduced nephrotoxic profile. Methodological quality was variable, with frequent unclear risks of bias related to blinding. Conclusion: Pre-clinical evidence robustly indicates that LNP encapsulation enhances the efficacy and safety of antifungal drugs in IPA models. These findings justify accelerated translational research to standardize formulations and advance the most promising candidates toward clinical trials for this high-mortality infection.

BackgroundMicrosporum canis is a primary causative agent of dermatophytosis. Its rising antifungal resistance necessitates the development of effective therapeutic alternatives. Although methylene blue-mediated photodynamic therapy (MB-PDT) is a promising strategy, a system-level understanding of its fungicidal mechanism is lacking.MethodsAn integrated multi-omics approach was employed, using data-independent acquisition (DIA) proteomics and untargeted metabolomics, to map the molecular response of clinical M. canis isolates to MB-PDT. Pathway enrichment analysis was performed to elucidate the key biological processes affected.ResultsMB-PDT induced multi-faceted molecular perturbations in M. canis. The treatment simultaneously disrupted membrane integrity by downregulating ergosterol biosynthesis (e.g., C4-methylsterol oxidase) and impaired the fungus’s antioxidant defenses by suppressing key enzymes such as glutathione S-transferase. Critically, the treatment suppressed secreted virulence factors essential for host invasion, including subtilisin-like protease 7. These disruptions led to a profound suppression of core biosynthetic machinery, with ribosome biogenesis and translation identified as the most significantly inhibited pathways. This resulted in a collapse of protein synthesis, energy production, and amino acid metabolism.ConclusionThe results indicate that the efficacy of MB-PDT stems from a multi-target mechanism that simultaneously damages cellular structures, attenuates virulence, and dismantles the fungus’s metabolic and translational capacity. This contrasts sharply with single-target conventional antifungals, providing a strong molecular rationale for its low potential to induce resistance. This study offers a comprehensive molecular blueprint for the action of MB-PDT against M. canis, strongly supporting its development as a durable therapeutic strategy for dermatophytosis.

PurposeThe purpose of this study was to evaluate the in vitro effects of combining rose bengal (RB) photodynamic antimicrobial therapy (PDAT) with conventional topical antifungals (amphotericin B, natamycin, and voriconazole) on clinical Fusarium and Aspergillus isolates and to determine the antifungal stability under experimental conditions.MethodsClinical isolates of Fusarium spp. (n = 3) and Aspergillus spp. (n = 3) were cultured using standard microbiology techniques. Agar plates were prepared with three concentrations of amphotericin B, natamycin, or voriconazole along with plates containing no antifungals. The following groups were tested in both dark and light conditions: (1) antifungal monotherapy (antifungal only), (2) RB monotherapy (RB only), and (3) antifungal and RB combination therapy. Plates were incubated for 7 days and percent growth inhibition was quantified. UV-visible spectroscopy and mass spectrometry was performed to assess antifungal stability.ResultsOverall, Fusarium isolates were more susceptible to RB-PDAT than Aspergillus isolates. RB-PDAT combination therapy with natamycin reduced growth inhibition, whereas combination therapy with voriconazole increased growth inhibition compared to antifungal monotherapy. UV-visible spectroscopy demonstrated 70% degradation of amphotericin B and full degradation of natamycin when combined with RB-PDAT, whereas voriconazole remained stable.ConclusionsAcross both Fusarium and Aspergillus isolates, treatment responses to antifungals with or without RB-PDAT demonstrated strain-specific effects. The increased fungal inhibition and maintained stability of voriconazole when combined with RB-PDAT highlight its potential compatibility with RB-PDAT. In contrast, the reduced inhibition and degradation of natamycin and amphotericin B with RB-PDAT suggests that drug stability may be a factor to consider when integrating RB-PDAT into fungal keratitis management.

Introduction. Fungal resistance hampers disease control and poses challenges in antifungal therapy. Combined therapies with broader spectrum of action and decreased side effects rate are needed. A synthetic antioxidant ethylmethylhydroxypyridine succinate could be a potential adjuvant for antifungals similar to its action when combined with antibacterial remedies. The aim of thіs work is the in vitro study of the susceptibility of Candida albicans reference strain to combined action of ethylmethylhydroxypyridine succinate with essential oils and specific antifungals from the groups of polyenes and azoles. Materials and methods. Sterile paper discs were impregnated with ethylmethylhydroxypyridine succinate (1000 μg/disc). Ten essential oils (10 μl) were studied alone or in a combination with it. Combinations of ethylmethylhydroxypyridine succinate with specific antimycotics was performed by applying its solution to standard discs with nystatin, amphotericin B, fluconazole, itraconazole and ketoconazole. The reference strain of C. albicans ATCC 10231 was used. The susceptibility was tested by the disc diffusion method and digital material was processed using computer program Microsoft Excel. Results. For ethylmethylhydroxypyridine succinate, the diameters of inhibition zones were 11.5-12.2 mm. The reference strain of C. albicans was susceptible to cinnamon and clove essential oils, dose-dependent susceptible to wormwood and rose oils and resistant to others. The combination of all essential oils with ethylmethylhydroxypyridine succinate enhanced the C. albicans susceptibility to these agents that characterized by an increase of inhibition zones by 3.5-13.0 mm. The C. albicans ATCC 10231 test culture was susceptible both to polyene antibiotics and azoles. When ethylmethylhydroxypyridine succinate combined with nystatin, an increase of the inhibition zone was 3 mm, with amphotericin B – 5 mm, fluconazole – 1.6 mm, itraconazole – 2.4 mm, ketoconazole – 5.4 mm. Conclusion. Thus, ethylmethylhydroxypyridine succinate, having no significant effect on the reference strain C. albicans ATCC 10231, enhanced the effect of conventional antifungals of various nature that can be a basis for new pharmaceutical compositions.

Introduction: Fungal infections caused by Candida glabrata have significantly increased in recent years, particularly in hospital settings, posing a serious public health issue due to their growing resistance to conventional antifungals, especially azoles. In response, combining conventional antifungal agents with natural compounds like essential oils represents an innovative and promising therapeutic strategy. Materials and Methods: This study aimed to evaluate the antifungal activity of fluconazole and Origanum vulgare essential oil, both individually and in combination, against a clinical strain of Candida glabrata isolated from a urinary sample at the Hassan II Regional Hospital in Agadir. The study employed two complementary approaches: the disk diffusion method and liquid microdilution, allowing for the determination of inhibition zones and minimum inhibitory concentrations (MIC) of each agent. Results: The results from the diffusion method indicated that fluconazole exhibited moderate activity with an inhibition zone of 29.5 ± 0.5 mm and an MIC of 8 µg/mL, while O. vulgare essential oil demonstrated marked antifungal activity, with an inhibition zone of 62 ± 0.5 mm and an MIC of 0.0435 mg/mL. The combination of both agents resulted in an increased inhibition zone and a significant reduction in their respective MICs, with a Fractional Inhibitory Concentration Index (FICI) of 0.5, indicating a synergistic effect between fluconazole and the essential oil. This combination resulted in a fourfold enhancement of fluconazole's antifungal activity. Conclusion: In conclusion, these findings suggest that Origanum vulgare essential oil could enhance the effectiveness of fluconazole against Candida glabrata, opening interesting perspectives for the development of new combined antifungal approaches, particularly in the context of resistance to conventional treatments.

Pythium insidiosum keratitis is an aggressive, vision-threatening corneal infection increasingly recognized across India, particularly among agricultural workers during monsoon season. Frequently misclassified as fungal keratitis, it responds poorly to conventional antifungals because the oomycete has a cellulose- and β-glucan–rich wall and lacks ergosterol, leading to therapeutic delay and rapid stromal melt. Indian cohorts have refined a practical diagnostic signature such as tentacular or reticular peripheral infiltrates with guttering, early endothelial plaque and hypopyon, and minimal satellite lesions. Calcofluor white and KOH show broad, ribbon-like, sparsely septate filaments; blood agar often grows colonies while Sabouraud shows scant growth; IVCM reveals thin, linear, right-angle branching hyphae; and PCR/ITS sequencing confirms species. Emerging immunology indicates early evasion of pattern-recognition receptors (TLR/CLR pathways) followed by dysregulated neutrophilic inflammation that accelerates collagenolysis. Management in India has converged on a surgery-first bias for deep or progressive disease early therapeutic keratoplasty with wide margins combined with targeted medical therapy: topical linezolid 0.2% and azithromycin 1% (± minocycline systemically), aggressive lubrication, and stromal melt mitigation (oral doxycycline, cautious steroids only post-control). Adjuncts include cyanoacrylate for impending perforation and intracameral/ intrastromal antibiotics in selected cases. Outcomes improve with rapid organism-specific therapy, meticulous peri-operative planning, and vigilant recurrence surveillance. India’s experience underscores priorities for the next decade: point-of-care diagnostics (LAMP/CRISPR), standardized drug susceptibility platforms, optimized peri-keratoplasty protocols, and host-directed immunomodulation to temper destructive inflammation without impairing clearance. This review synthesizes epidemiology, clinical diagnostics, immunopathogenesis, and management, translating India-derived insights into a pragmatic framework for regions confronting the global spread of Pythium keratitis.

Natural metabolites produced by lactic acid bacteria (LAB) are emerging as sustainable alternatives to synthetic antifungal agents. This study evaluated the antifungal and antibiofilm activities of cell-free supernatants (CFSs) derived from Lactiplantibacillus plantarum S61, cultivated with glucose (CFS-Gl) or arabinose (CFS-Ar), against the spoilage and opportunistic yeast Rhodotorula glutinis UMP22. Antifungal activity was determined by agar diffusion and MIC/MFC assays, while stability was assessed under variable temperature, pH, and enzymatic conditions. Membrane permeability, evaluated through propidium iodide uptake, confirmed that CFSs disrupt fungal cell integrity, indicating a multifactorial mode of action involving organic acids and protease-sensitive peptides.CFS-Ar exhibited significantly higher antifungal potency than CFS-Gl, achieving an inhibition zone of 36.7 ± 0.4 mm. When combined with sub-inhibitory concentrations of cycloheximide (MIC/2 = 15.5 μg/mL; MIC/3 = 10.3 μg/mL), both CFSs produced a synergistic effect, achieving near-complete growth suppression while lowering the required antifungal dose. In addition, both CFSs demonstrated strong preventive and curative antibiofilm activities across a wide range of temperatures (4–37 °C), concentrations, and exposure durations. The persistence of activity under refrigeration highlights their relevance for food preservation.Overall, these findings identify L. plantarum S61 as a promising source of thermostable, pH-tolerant bioactive metabolites with dual antifungal and antibiofilm functions. The observed synergy between CFSs and conventional antifungals offers an innovative, eco-friendly, and resistance-mitigating strategy for controlling spoilage yeasts and emerging fungal contaminants in food and health-related applications.

Silver nanoparticles (AgNPs) have gained prominence in the scientific literature as potential antifungal therapeutic agents, especially those obtained through biological synthesis, due to their superior physicochemical properties. This review examines formulations and patents incorporating AgNPs with antifungal activity, focusing on their applicability in the treatment of mycoses, particularly in vivo. Comparative data on the mechanism of action of AgNPs in planktonic cells and biofilms are presented, as well as transcriptional analyses in fungi exposed to these nanoparticles. The results demonstrate that formulations containing AgNPs have been applied in various contexts, such as wound dressings, in combination with pharmaceuticals, dental products, and cosmetics, reflecting the growing search for therapeutic alternatives, especially for superficial infections. In experimental models, AgNPs demonstrate applicability in the treatment of dermatomycoses and opportunistic mycoses, promoting healing, low toxicity, and reducing fungal load. They can be used alone or in combination with conventional antifungals. Although still poorly understood, the impact of AgNPs on fungal gene expression suggests modulation of virulence, with potential relevant therapeutic implications. The antifungal activity of AgNPs is effective, although the required concentration varies depending on the target - planktonic cells or biofilms. These data highlight the importance of expanding studies to other fungal pathogens.

Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans are the invasive fungi whose diseases are becoming a growing health issue in the global community, particularly in immunocompromised people. The increasing resistance of the conventional antifungals and the shortage of the existing treatment methods require alternative methods. The present review is an evaluation of the antifungal activity of metal-based nanoparticles, including silver (Ag), copper (Cu), zinc oxide (ZnO), titanium dioxide (TiO2), and selenium (Se) in relation to the three predominant pathogenic fungi. It also talks about their mode of action, relative efficacy, toxicity and their possible future clinical use. Multimodal effects of metal nanoparticles are reactive oxygen species (ROS) formation, membrane destabilization, and enzyme inhibition, and biofilm disruption. Silver and zinc oxide nanoparticles are very effective against C. albicans particularly in biofilm-associated infections. Copper and titanium dioxide nanoparticles also work against A. fumigatus and selenium nanoparticles have been encouraging against C. neoformans including blood-brain barrier penetration. Toxicity comparison reveals variations, with ZnO and TiO2 demonstrating favorable biocompatibility. Metal nanoparticles can serve as effective alternatives to traditional antifungal agents, particularly for drug-resistant and biofilm-associated infections. Their physicochemical versatility and ability to target various fungal structures favor their potential integration into next-generation antifungal strategies, pending further optimization to ensure safety and regulatory approval.

Candidiasis is acommon infection primarily caused by the opportunisticfungus Candida albicans. Conventional antifungals have been associated with several limitations,and today, antimicrobial photodynamic therapy (aPDT) is raised asan adjuvant treatment. This study aimed to develop a carrier systemfor the photosensitizer methylene blue (MB) based on a gellan gum(GG) hydrogel, a nontoxic exopolysaccharide. Two formulations consistingof 0.6% and 1.0% (w/v) GG containing MB were prepared and characterizedin relation to release kinetics, absorption spectroscopy, and opticalshield formation. Then, the effects of MB GG formulations in aPDTusing LED irradiation were evaluated against C. albicans. For this, aPDT was applied toC. albicans in planktonic and biofilm stages and also tested in a Galleria mellonella burn infection model. The successfulincorporation of MB into the GG hydrogel was confirmed by absorptionspectroscopy, with a characteristic peak at 660 nm for intact MB andboth GG formulations. The GG0.6% hydrogel released 100% of MB in 12min, whereas the GG1.0% hydrogel released only 75% of MB after 25min. Furthermore, no optical shield formation was noticed with theMB gellan formulations in comparison to the aqueous form. In relationto antifungal activity on C. albicans, aPDT with GG0.6% and GG1.0% containing MB led to an eradicationof planktonic cells and a partial reduction of biofilms, as observedin aPDT with MB aqueous. When aPDT was applied in G.mellonella larvae, an increase of 50% and 30% in survivalrate was found, respectively, for the groups treated with MB gellanformulation and MB aqueous. In conclusion, the gellan gum formulationsdesigned here were able to release MB and maintain its optical andphotodynamic properties against C. albicans. In addition, aPDT with MB gellan formulations had higher in vivoefficacy than MB aqueous.

Multidrug-resistant Candida infections demand urgent therapeutic solutions. This study demonstrated the green synthesis of silver nanoparticles designated At-AgNPs using Alkanna tinctoria root extract, showing enhanced antifungal activity against Candida species including resistant C. auris. Characterization confirmed spherical At-AgNPs with 19.91 nm diameter by TEM and 120.6 nm hydrodynamic size, exhibiting a UV-Vis peak at 406.27 nm. EDX analysis revealed 79.24% silver content, while XRD patterns verified face-centered cubic crystallinity. The nanoparticles maintained excellent stability with zeta potential measuring − 23.34 mV and PDI 0.202. At-AgNPs displayed strong antifungal effects, particularly against C. parapsilosis showing 15.46 mm inhibition zone with MIC and MFC values of 1.0 and 2.0 mg/L respectively. Notable synergy emerged when combining At-AgNPs with conventional antifungals, especially clotrimazole against C. albicans demonstrating 37.28 mm inhibition compared to 33.84 mm for clotrimazole alone. SEM imaging revealed extensive morphological damage to fungal cells following combination treatment. These results position At-AgNPs as a viable adjunct therapy capable of boosting conventional treatment effectiveness while potentially lowering required drug doses and minimizing side effects in resistant Candida infections.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-19831-9.