Search Results (5,367)

Background/Objectives: The present study investigates the antifungal potential of 1,5-diarylidene-4-piperidones. Methods: These compounds were synthesized via Claisen–Schmidt condensation, and their antifungal efficacy was tested against Cryptococcus neoformans, a yeast recently qualified as a critical priority pathogen by the World Health Organization, through determination of their minimum inhibitory concentration (MIC). We designed and synthesized a series of piperidones to explore structure–activity relationships. Results: Systematic modification of the substituent pattern revealed that tetrabutoxy groups exhibited potent activity (MIC of 7.8 µM), surpassing standard antifungals like fluconazole. The selectivity index (SI) values confirmed their safety profile across various human cells. Docking analysis demonstrated that these compounds target sterol 14-demethylase, suggesting potential inhibition of ergosterol synthesis as a mechanism of action. Interestingly, the compounds also demonstrated broad-spectrum activity against other pathogenic yeasts and fungi, including Candida and Aspergillus species, and against fluconazole-resistant strains. Conclusions: These findings underscore the potential of 1,5-diarylidene-4-piperidones as promising antifungal candidates with a favorable safety profile. Full article

Six aromatic plants (Lavandula pedunculata subsp. sampaioana, Lavandula stoechas subsp. luisieri, Mentha × piperita, Origanum vulgare subsp. virens, Thymus mastichina, and Thymus zygis subsp. sylvestris) were analyzed to evaluate their essential oil (EO) yield, chemical composition, antioxidant activity, and antifungal capacity against two mold species, green mold (Penicillium digitatum) and blue mold (Penicillium italicum). The antioxidant activity was evaluated using the ABTS and DPPH methods, and the antifungal activity was determined using the disk diffusion method. The results of the antioxidant activity tests showed that the essential oil of Th. zygis subsp. sylvestris has the highest value for the ABTS method (161.70 ± 0.15 mM TROLOX eq. and 864.20 ± 0.81 g TROLOX eq/g EO) and the L. stoechas subsp. luisieri essential oil in the DPPH method (33.91 ± 1.21 mM TROLOX eq. and 184.99 ± 6.58 g TROLOX eq/g EO). Furthermore, the essential oils with lower antioxidant activity were L. pedunculata subsp. sampaioana for the ABTS method (3.84 ± 0.26 mM TROLOX eq. and 20.79 ± 1.41 g TROLOX eq/g EO) and Th. mastichina for DPPH method (0.96 ± 0.03 mM TROLOX eq. and 5.31 ± 0.16 g TROLOX eq/g EO). Th. zygis subsp. sylvestris exhibited the strongest antifungal activity, with medium inhibition halo values of 60.50 ± 5.77 mm and 54.33 ± 2.93 mm for P. digitatum and P. italicum, respectively. Full article

Invasive infections caused by rare moulds (RM) are increasingly reported and often exhibit resistance to antifungal agents. Their epidemiology varies regionally, yet data from Greece are scarce. To address this gap, we conducted a 15-year retrospective study of RM fungaemia at a tertiary academic hospital in Athens, Greece. All microbiologically confirmed cases in hospitalised patients between 2010 and 2024 were reviewed. Demographic and clinical data were retrieved from medical records. Incidence rates were calculated per 1000 admissions and 10,000 bed-days. Isolates were morphologically identified and, when available, molecularly characterised and tested for antifungal susceptibility according to EUCAST guidelines. Eight RM fungaemia episodes (0.8% of total fungaemias) were identified, with an incidence of 0.01/1000 admissions and 0.03/10,000 bed-days, without bacterial co-infections. Haematological malignancies (62%) were the most common underlying condition. Fusarium spp. were the predominant pathogens (6/8), followed by single cases due to Lomentospora prolificans and Acremonium spp. Amphotericin B showed the highest in vitro activity against Fusarium isolates (MIC 0.5–1 mg/L), followed by voriconazole (MICs 2–8 mg/L) whereas other azoles showed no in vitro activity (MICs ≥ 8 mg/L). Half of the infections were breakthrough, whereas in 3/8 cases, the diagnosis was established post-mortem (n = 2) or post-discharge. Among the five patients who received treatment, the crude mortality rate was 60%. This first epidemiological report on RM fungaemia in Greece highlights the predominance of Fusarium spp., the frequency of breakthrough infections, and the challenges in early diagnosis and management. Increased clinical awareness and regional surveillance are essential for optimising outcomes. Full article

The continuous increase in microbial resistance to therapeutic agents has become one of the greatest challenges to global health. In this context, the present study investigated the bioactivity of 25 chroman-4-one and homoisoflavonoid derivatives—17 of which are novel—against pathogenic microorganisms, including Staphylococcus epidermidis, Pseudomonas aeruginosa, Salmonella enteritidis, Candida albicans, C. tropicalis, Nakaseomyces glabratus (formerly C. glabrata), Aspergillus flavus, and Penicillium citrinum. Antimicrobial assay was performed using the microdilution technique in 96-well microplates to determine the minimum inhibitory concentration (MIC). Thirteen compounds exhibited antimicrobial activity, with compounds 1, 2, and 21 demonstrating greater potency than the positive control, especially against Candida species. Molecular modeling suggested distinct mechanisms of action in Candida albicans: 1 potentially inhibits cysteine synthase, while 2 and 21 possibly target HOG1 kinase and FBA1, key proteins in fungal virulence and survival. Our findings indicated that the addition of alkyl or aryl carbon chains at the hydroxyl group at position 7 reduces antimicrobial activity, whereas the presence of methoxy substituents at the meta position of ring B in homoisoflavonoids enhances bioactivity. These findings highlight key structural features of these compound classes, which may aid in the development of new bioactive agents against pathogenic microorganisms. Full article

Aspergillus fumigatus is an opportunistic filamentous fungus that primarily affects the respiratory tract of the human body. Depending on its host’s immune response, the pathogen can cause invasive pulmonary aspergillosis (IPA). Biofilm formation by A. fumigatus increases virulence and resistance against antifungals and immune response and is one important factor in IPA development. Here, two human-like models, precision cut lung slices (PCLS) and a biofilm co-culture model, have been developed to test the anti-biofilm activity of voriconazole, amphotericin B, as well as luliconazole against A. fumigatus. In both assays, metabolically active A. fumigatus biofilms were examined at different biofilm developmental stages using an XTT assay. A decrease in the metabolic activity of the fungal biofilms was detected for each of the tested agents in both assays. Significant anti-biofilm effects exist against early-stage biofilm in the co-culture model. In the PCLS assay, amphotericin B showed the strongest inhibition after 24 h. In conclusion, the applied PCLS ex vivo model can be used to study the property and activity of certain antifungal compounds against Aspergillus biofilm. With its close resemblance to human conditions, the PCLS model has the potential for improving the current understanding of biofilm treatments in laboratory settings. Full article

Tomato fruit is susceptible to decay caused by Colletotrichum gloeosporioides. An edible coating derived from essential oils loaded into a chitosan polysaccharide polymer is a sustainable delivery approach to improve coating versatility and stability for reduced reliance on synthetic fungicides to combat anthracnose incidence in tomatoes. The objective of this study was to evaluate the antifungal efficacy of nanostructured thyme essential oil incorporated into chitosan coatings [Nano-(T)-EO-CS] against Colletotrichum gloeosporioides in tomato fruits, and to investigate the underlying mechanisms contributing to its inhibitory effects. Nano-(T)-EO of (1% v/v) showed the greatest antifungal activities while achieving complete inhibition of C. gloeosporioides. At (0.8% w/v) concentration, chitosan inhibited 78% of radial mycelial growth in C. gloeosporioides. Loading Nano-(T)-EO (1% v/v) into chitosan (0.8% w/v) completely inhibited spore germination (100%). The surface electron microscopy revealed that the Nano-(T)-EO-CS coating induced significant deformation and inhibited the growth of C. gloeosporioides. Compared with the control, the Nano-(T)-EO-CS coating reduced disease incidence by 50%, whereas the commercial antifungal agent Sporekill^® reduced incidence by 40% in preventively inoculated tomatoes stored at 10 °C and 85% relative humidity (RH) for 14 days after harvest, and at 18 °C for 3 days at the market shelf condition. Despite chitinase activity peaking on day 14 of cold storage, it peaked significantly on day 7 in Nano-(T)-EO-CS and Sporekill^®-treated tomatoes. The Nano-(T)-EO-CS coating enhanced ferric-reducing antioxidant power and total phenol content in tomatoes for 7 and 14 d of postharvest storage. The chitosan-based edible coating loaded with thyme essential oil offers a sustainable, eco-friendly alternative to chemical fungicides for improving tomato shelf life and reducing decay. Full article

Oil-in-water emulsions are widely used to enhance the solubility, stability, and bioactivity of essential oils in aqueous systems. Advancing the functionality and sustainability of these emulsions using renewable, eco-friendly ingredients remains an important research focus. This study developed and evaluated a lemongrass essential oil nanoemulsion stabilized by Tween 80, NaCl, and soybean stover-derived cellulose nanocrystals. After freeze-drying, the nanoemulsion was redispersed in water and analyzed for particle size, zeta potential, polydispersity index, and essential oil recovery. Freeze-drying led to significant bioactivity losses, with antifungal and antioxidant activities reduced by 77% and 31%, respectively. Antioxidant activity declined rapidly within the first two weeks of storage at room temperature but was not significantly impacted by light exposure. Storage conditions also altered the sample composition, with one new compound detected in samples stored without light exposure and eleven new peaks observed in light-exposed samples. This study provides insights into the effects of freeze-drying and storage on lemongrass essential oil-loaded nanoemulsion stabilized by Tween 80, NaCl, and cellulose nanocrystals. The findings highlight the challenges of preserving bioactivity and composition in lyophilized essential oil-loaded emulsions and suggest avenues for optimizing drying processes and formulations to improve storage stability and efficacy. Full article

Background: Prosthetic candidiasis remains a significant clinical challenge, particularly due to the ability of Candida species to form resilient biofilms on dental prostheses, which limits the efficacy of conventional antifungal treatments. In this context, developing strategies to prevent or reduce biofilm formation is essential. Objectives This study investigates the antifungal and antibiofilm potential of a hydrogel formulation incorporating aminochalcone AM-35 as a candidate for the prevention and treatment of prosthetic candidiasis. Methods: To achieve this, experiments were conducted to determine the minimum inhibitory concentration (MIC) of aminochalcone AM-35 against Candida albicans and Candida tropicalis strains. AM-35 was incorporated into a hydrogel, which was subsequently tested on biofilms formed by these yeast species, both individually and in combination. The experimental disks were sterilized and incubated with C. albicans, C. tropicalis, and a mixture of both strains for 120 h to allow biofilm maturation. After contamination, the samples were divided into four experimental groups: Group 1: Hydrogel; Group 2: Hydrogel+AM-35; Group 3: Sodium hypochlorite (positive control); and Group 4: No treatment. The samples were then subjected to a sonication process to disaggregate the cells, which were then cultured on plates for colony-forming unit (CFU/mL) counts. The hydrogel’s toxicity was evaluated in vivo using the Galleria mellonella model. Results: The hydrogel formulation demonstrated significant antimicrobial activity, with an MIC of 7.8 μg/mL for C. albicans and 3.9 μg/mL for C. tropicalis. Treatment with the hydrogel at a concentration of 39 μg/mL resulted in a significant reduction in the formation and viability of mixed-species biofilms (p < 0.05). Additionally, the results indicated robust activity against C. albicans and C. tropicalis without presenting toxicity in the Galleria mellonella model. In conclusion, the hydrogel formulation exhibited effective antibiofilm activity, significantly reducing the microbial load. Conclusions: These findings open new possibilities for the development of alternative treatments for prosthetic candidiasis. The research suggests that the use of chalcone-based compounds may represent a promising approach in combating fungal infections in dentistry. Full article

The research aimed to study the genome of Cryptococcus neoformans isolated from bird excreta. Thirteen isolates were cultured, colony stained, and underwent biochemical testing confirmation by nested polymerase chain reaction using ITS1-ITS4 and CN4-CN5 primers, respectively. Antifungal susceptibility testing and whole-genomic sequencing were analyzed. The results determined that all isolates were susceptible to amphotericin B (100%), fluconazole, and itraconazole (92.3%). One isolate (DOP3) showed resistance to fluconazole and itraconazole (MIC >64 and >8 µg/mL, respectively). A phylogenetic tree showed the identity of C. neoformans (serotype A). The genome of resistant (DOP3) and non-resistant isolates (DOP3.1) had 14 chromosomes. DOP3 consisted of 38 candidate antifungal resistance genes, which were the most active against azoles (14). The annotated genes in the azole group mostly were in the ATP-binding cassette transporter transmembrane superfamily. Resistance genes against FCZ were in the transcription factors (HAP2, HAP5), zinc finger (NRG1), cytochrome P450 (ERG11), and Myb-like DNA-binding domain (REB1). The most frequent resistance genes against ITZ were cytochrome P450 (ERG5 and ERG11) and a transcription factor (HAP5). DOP3.1 also consisted of 26 candidate resistance genes against azoles. Resistance genes against the azole group belong to the ABC transporter transmembrane superfamily. Resistance genes against FCZ belong to cytochrome P450 (ERG11), the zinc finger (NRG1), and the CCAAT binding transcription factor (HAP2). Resistance genes belonging to cytochrome P450 (ERG5) were found against ITZ. This research provides the first report of C. neoformans (serotype A) in zebra dove excreta, drug susceptibility to a resistant strain, and identification of resistance genes. Farm sanitation should be strictly applied, and immunocompetent people should avoid contact with zebra dove excreta. Full article

Biological control serves as a crucial strategy for crop disease management. The biocontrol potential and plant growth-promoting effects of the strain YTBTa14 were investigated. Genetic sequencing confirmed YTBTa14 as Pseudomonas chlororaphis, which exhibited broad-spectrum antifungal activity against multiple pathogens affecting grapevine, apple, cherry, and wheat. YTBTa14 significantly enhanced the growth of wheat and grapevine, specifically increasing wheat seed germination rates and improving root and coleoptile development. In grapevine plant, significant increases in root length, stem length, and fresh weight were observed. The strain demonstrated robust adaptability and stable antagonism under varying sodium chloride (NaCl) concentrations, pH levels, and temperatures. YTBTa14 modulated plant hormone levels, elevating the content of indole-3-acetic acid (IAA), gibberellins (GA), and cytokinins (CTK). Furthermore, it effectively stimulated the production of key plant defense enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Pretreatment of grape leaves with YTBTa14 triggered plant cell defense response and upregulated the expression of defense-related genes PR1 (pathogenesis-related protein 1) and PAL1 (phenylalanine ammonia-lyase 1), thereby mitigating the severity of downy mildew disease and inducing systemic resistance. These findings demonstrate that YTBTa14 is a highly promising candidate for development as a multifunctional agricultural biocontrol agent. Full article

Plant growth-promoting rhizobacteria (PGPR) offer a sustainable strategy for enhancing crop productivity and suppressing phytopathogens. In this study, seven bacterial isolates obtained from the rhizosphere of healthy tomato plants were evaluated for their antagonistic activity against the fungal pathogen Passalora fulva, the leaf miner Tuta absoluta, and their effects on tomato growth. In vitro dual-culture assays revealed that isolates IQR1, IQR2, IQR3, and IQR5 significantly inhibited P. fulva mycelial growth, with inhibition rates exceeding 35%. Volatile organic compounds (VOCs) produced by the bacterial isolates exhibited considerable antifungal activity, with IQR5, IQR1, and IQR2 achieving over 84% inhibition. Molecular identification based on 16S rDNA sequencing indicated that these isolates belong to distinct taxa: Leucobacter aridicolis (ON799334.1) (genus Leucobacter), Paenochrobactrum sp. (JF804769.1) (genus Paenochrobactrum), an uncultured bacterium (JQ337400.1) (genus Psychrobacter), and marine bacterium AK6_052 (KF816539.1) (genus Brevundimonas). Under greenhouse conditions, isolates IQR3, IQR5, and IQR1 reduced disease incidence of P. fulva to 20–26%. The same isolates also promoted plant growth, enhancing stem height and collar diameter. In addition, IQR5 significantly reduced T. absoluta larval density and foliar damage, with the number of larvae per leaflet decreasing to 1.42, compared to 3.20 in the control. These findings highlight the potentials of these rhizobacterial strains—particularly IQR5—as effective biocontrol agents and biofertilizers for integrated pest and disease management in tomato cultivation. Full article

Background: Tacrolimus is a cornerstone of immunosuppressive therapy following heart transplantation. Despite routine therapeutic drug monitoring (TDM), substantial interindividual variability in tacrolimus pharmacokinetics presents a persistent challenge. Pharmacogenetic profiling—particularly of CYP3A5 and CYP3A4 polymorphisms—offers a promising approach to individualize tacrolimus dosing and improve clinical outcomes. Case Presentation: We describe a 54-year-old male heart transplant recipient with persistently subtherapeutic tacrolimus trough concentrations despite escalating standard doses. Tacrolimus dosing initially started at 3.5 mg twice daily, escalated to 7.0 mg twice daily, with final maintenance dosing at 6.5 mg twice daily. TDM values were persistently subtherapeutic at 3–5 ng/mL for over a month before achieving therapeutic targets >10 ng/mL. Pharmacogenetic testing revealed a CYP3A5 expresser genotype (*1/*3) and normal CYP3A4 activity (*1/*1), suggesting enhanced metabolic clearance. In accordance with CPIC guidelines, tacrolimus dosing was intensified and supported by co-administration of diltiazem (60 mg twice daily, later adjusted to 90 mg twice daily), a CYP3A4 inhibitor. Subsequent TDM confirmed achievement of therapeutic levels. At nine months post-transplant, the patient exhibited stable graft function and excellent clinical status. Discussion: This case underscores the value of genotype-informed tacrolimus dosing in clinical scenarios where standard TDM is insufficient. Pharmacogenetic variation—particularly involving CYP3A5 expression—has been consistently associated with altered tacrolimus exposure and dose requirements. The literature supports routine genotyping in solid organ transplant recipients, although implementation remains limited. Additional considerations include drug–drug interactions, notably with CYP3A-modulating agents such as diltiazem and antifungals, which may further influence tacrolimus pharmacokinetics. Current evidence suggests that the utility of CYP3A4 genotyping may be phase-dependent, being more impactful during early post-transplant periods. Conclusions: Incorporating pharmacogenetic data alongside TDM facilitates more precise and individualized tacrolimus therapy, optimizing immunosuppressive efficacy and minimizing risk. This case, supported by literature review, advocates for broader integration of genotype-guided strategies in transplant pharmacotherapy. Full article

Thermo-tolerance is a virulence factor responsible for the emergence of new fungal pathogens, including Candidozyma auris (formerly classified as Candida auris, C. auris). It has been shown that in C. auris the thermo-tolerance, as well as other virulence traits, such as the ability to aggregate, to form pseudo-hyphae, or to produce melanin are strain-specific features. Here, we investigated the impact of different temperatures (25 °C, 37 °C and 42 °C) on the phenotypic and virulence profile of C. auris strain CDC B11903. The results show a positive correlation between the resistance to antifungals and increasing temperature from 25 °C to 37 °C, while no differences were observed between 37 °C and 42 °C, except for Anidulafungin. Furthermore, C. auris growth was impaired at 25 °C as compared to 37 °C and 42 °C. Except for the haemolytic activity, which increased with rising temperatures, phospholipase, lipase and biofilm production were found at all tested temperatures. Moreover, the ability to produce melanin was observed only at 37 °C and 42 °C. The capacity to grow as pseudo-hyphae or in clusters and to adhere to both biotic and abiotic surfaces were observed at all the temperatures tested, with increased propensity of C. auris to adhere to abiotic surfaces with rising temperatures. The results underline the thermo-tolerance of C. auris strain B11903 and its increased virulence profile at human body temperature both in physiological (37 °C) and febrile state (42 °C). Full article

Trichothecenes are a family of toxic metabolites produced by multiple fungal species. All trichothecene analogs include an epoxide-containing tricyclic structure known as 12,13-epoxytrichothec-9-ene (EPT) but differ by the presence, absence and types of substituents attached to EPT. Among the 21 known genes associated with trichothecene biosynthesis, tri14 is one of only three that are universally found in all trichothecene-producing fungi. Recent studies have revealed that the tri14-encoded protein, Tri14, enhances the biosynthetic reaction that forms EPT, a reaction previously thought to occur spontaneously. In our study, we assessed the impact of tri14 deletion on the biology of Trichoderma arundinaceum, a producer of the trichothecene harzianum A (HA). The results revealed that tri14 deletion reduced HA production by 69%, an outcome that was associated with diminished antifungal activity. To our knowledge, this is the first study showing that tri14 is required for wild-type production of a trichothecene analog by a fungal organism. tri14 deletion also had moderate effects on the expression of some other trichothecene biosynthetic genes, as well as in the production of metabolites beyond HA. These results suggest that Tri14 plays a crucial role in EPT formation, leading to diverse downstream effects on the biology of T. arundinaceum. Full article

Mold-active prophylaxis has reduced the incidence of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies (HMs), but breakthrough IPA (Bt-IPA) is increasingly encountered. Therefore, we studied determinants of Bt-IPA risk and its prognostic significance. We retrospectively reviewed culture-positive proven/probable IPA cases in HM patients at MD Anderson Cancer Center (2016–2021). Bt-IPA and non-Bt-IPA cases were compared to characterize risk factors, clinical presentation, and outcomes. Independent predictors of 42-day all-cause mortality were assessed using propensity score-adjusted Cox regression. Among 118 IPA cases, 50 (42.4%) were Bt-IPA. Bt-IPA was associated with acute leukemia/myelodysplastic syndrome, active HM, severe neutropenia (<100/mm³), and graft-versus-host diseases. Uncommon Aspergillus species (non-fumigatus, flavus, terreus, or niger) were more frequent in Bt-IPA than non-Bt-IPA (20.4% vs. 4.8%, p = 0.010). Forty-two-day mortality was higher in Bt-IPA (65.3% vs. 37.3%, p = 0.003), but Bt-IPA itself was not an independent predictor or mortality (p = 0.064), which was instead driven by neutropenia (p = 0.020) and hypoalbuminemia (p = 0.002). In conclusion, Bt-IPA accounted for nearly half of contemporary IPA cases and was linked to host-related risk factors and the recovery of uncommon Aspergillus species. Although not an independent prognostic predictor, Bt-IPA reflected poor host status. Thus, early diagnosis, immune enhancement strategies, and effective first-in-class antifungals may improve outcomes. Full article