Antifungal Efficacy Research Articles

The Antifungal Effects of Berberine and Its Proposed Mechanism of Action Through CYP51 Inhibition, as Predicted by Molecular Docking and Binding Analysis

Fungal infections present a significant health risk, particularly in immunocompromised individuals. Berberine, a natural isoquinoline alkaloid, has demonstrated broad-spectrum antimicrobial activity, though its antifungal potential and underlying mechanisms against both yeast-like and filamentous fungi are not fully understood. This study investigates the antifungal efficacy of berberine against Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, and Trichophyton mentagrophytes in vitro, as well as its therapeutic potential in a murine model of cryptococcal infection. Berberine showed strong antifungal activity, with MIC values ranging from 64 to 128 µg/mL. SEM and TEM analyses revealed that berberine induced notable disruptions to the cell wall and membrane in C. neoformans. No signs of cell necrosis or apoptosis were observed in fungal cells treated with 2 × MIC berberine, and it did not increase intracellular ROS levels or affect mitochondrial membrane potential. Molecular docking and binding affinity assays demonstrated a strong interaction between berberine and the fungal enzyme CYP51, with a dissociation constant (KD) of less than 1 × 10−12 M, suggesting potent inhibition of ergosterol biosynthesis. In vivo studies further showed that berberine promoted healing in guinea pigs infected with T. mentagrophytes, and in a murine cryptococcal infection model, it prolonged survival and reduced lung inflammation, showing comparable efficacy to fluconazole. These findings indicate that berberine exerts broad-spectrum antifungal effects through membrane disruption and CYP51 inhibition, highlighting its potential as a promising therapeutic option for fungal infections.

A Review on Green Synthesized Metal Nanoparticles Applications

Nanotechnology pertains to the manipulation of materials at exceedingly small scales, specifically between 1 and 100 nanometers. Materials at this scale exhibit significantly different properties compared to the same materials at larger scales. An emerging trend is the utilization of nanoparticles (NPs) to address environmental issues. Metallic nanoparticles are among the several nanoparticles that are extensively utilized in environmentally sustainable endeavors. A sustainable, economical, and enduring approach is to synthesize nanoparticles through a more ecologically friendly procedure instead of a physical or chemical method. Plant components primarily function as reducing and capping agents in eco-friendly synthesis. Diverse metallic nanoparticles of various sizes and shapes have been created utilizing extracts from plant materials, including leaves, bark, fruits, and flowers. The synthesis of Nobel laureate metal nanoparticles is essential to the medical sector. A diverse array of glycosides and phenolic compounds constitutes numerous organic constituents in plants, facilitating the synthesis of metal nanoparticles. The absence of detrimental by-products in metal nanoparticle synthesis is the primary significance of green synthesis. The nanoparticles generated by an eco-friendly approach demonstrate several significant biological activity. A substantial body of literature demonstrates that the synthesized nanoparticles are efficacious against both gram-positive and gram-negative bacteria, including E. coli, Bacillus subtilis, Klebsiella pneumoniae, and Pseudomonas fluorescens. The synthesized nanoparticles not only display antifungal efficacy against several cancer cell lines, including those of breast cancer, but also demonstrate antifungal activity against Trichophyton simii, Trichophyton mentagrophytes, and Trichophyton rubrum. Moreover, they exhibit potent antioxidant properties. The dimensions and morphology of these metal nanoparticles substantially influence their functionalities. Particles characterized by a large surface area and diminutive size provide significant potential for medical applications. This paper aims to provide a comprehensive summary of current advancements in the synthesis of nanoparticles utilizing biological entities and their numerous potential applications.

Bacterial Allies in Agricultural Defense: Evaluating Xenorhabdus and Photorhabdus Supernatants Against Phytophthora infestans and Monilinia laxa

Fungal plant pathogens represent a significant threat to global agriculture, affecting crop productivity and food security. Phytophthora infestans and Monilinia laxa are two such pathogens causing blights and brown rot, respectively, in economically vital crops like potato and stone fruits. Developing sustainable management strategies is crucial to mitigate these threats. Xenorhabdus and Photorhabdus bacteria produce various secondary metabolites with different biological activities. This study investigates the antifungal activity of cell-free supernatants from Xenorhabdus and Photorhabdus bacteria against P. infestans and M. laxa. Results demonstrate varying degrees of antifungal efficacy among bacterial species, with X. cabanillasii and X. szentirmaii exhibiting significant suppression of fungal growth. The findings underscore the importance of exploring biocontrol agents in integrated pest management practices.

Antifungal activities of Pediococcus pentosaceus LWQ1 and Lactiplantibacillus plantarum LWQ17 isolated from sourdough and their efficacies on preventing spoilage of Chinese steamed bread

The short shelf life of Chinese steamed bread (CSB) at room temperature due to moldy contamination restricts its popularity. This study aimed to evaluate two selected lactic acid bacteria strains, namely Lactiplantibacillus plantarum LWQ17 (LWQ17) and Pediococcus pentosaceus LWQ1 (LWQ1), on their antifungal activities and potential applications in CSB making. The results showed that both strains, especially LWQ17, displayed remarkable inhibition against Aspergillus niger and Penicillium polonicum, the representative species found in CSB spoilage. LWQ17 and LWQ1 destroyed the cell membranes of the fungi and caused a loss of intracellular substances. When applied in CSB making, both strains could delay the germination of mold on the surface of CSB in a season-dependent way. LWQ17 delayed the germination of mold by 4 d in Spring and Winter, while 1 d in Summer and Autumn. Further study revealed that their antifungal activities were greatly influenced by temperatures and humidity. Both strains could completely inhibit the germination of mold during two weeks of storage under 37 °C but with different humidity levels. Moreover, our results demonstrated that acidic substances were crucial in inhibiting the fungi, while proteinic substances and hydrogen peroxide played an auxiliary role. Analysis of their acids by targeted metabolomics showed that LWQ17 produced more kinds of acids, and the amount of phenyllactic acid produced by LWQ17 was 60 times higher than that produced by LWQ1, which may explain its better antifungal efficacy. This study provides a reference for employing lactic acid bacteria in CSB preservation under different conditions.

Antifungal Efficacy of Ultrashort β-Peptides against Candida Species: Mechanistic Understanding and Therapeutic Implications.

Candidiasis, a condition spurred by the unchecked proliferation of Candida species, poses a formidable global health threat, particularly in immunocompromised individuals. The emergence of drug-resistant strains complicates management strategies, necessitating novel therapeutic avenues. Antimicrobial peptides (AMPs) have garnered attention for their potent antifungal properties and broad-spectrum activity against Candida species. This study assessed the antifungal effectiveness of ultrashort β-peptides against Candida strains, with a specific focus on peptide P3 (LAU-β3,3-Pip-β2,2-Ac6c-PEA). Our findings showed P3's remarkable fungistatic and fungicidal activities against Candida albicans, exhibiting an MIC of 4 μg/mL, comparable to those of standard antifungal drugs. The MIC value remained unchanged in the presence of ADC and BSA, indicating that serum albumin does not diminish the activity of P3. P3 demonstrates synergistic effects when combined with Fluconazole (FLU), Itraconazole (ITR), and Nystatin (NYS) to the extent that it becomes effective at 0.125, 0.125, and 0.03125 μg/mL, respectively. Concentration versus time-kill kinetics showed its time-dependent activity up to the first 12 h against C. albicans, and later concentration also played a role; indeed, at 24 h the whole culture was sterilized at 8× MIC. Post-antifungal effect assays confirmed prolonged suppression of pathogen growth after the removal of P3 from the media for significant durations. More importantly, P3 inhibits hyphae formation and biofilm development of Candida, outperforming Fluconazole with respect to these properties. Mechanistic insights display P3's potential to disrupt fungal cell membrane integrity and dose-dependent inhibition of ergosterol biosynthesis, essential for fungal cell wall integrity. Using the Bradford assay, it was observed that extracellular protein concentrations increased with higher doses of the compound, thereby validating the effect of P3 on membrane integrity. A comparative gene analysis using RT-PCR showed that P3 downregulates ERG3, ERG11, and HWP1, which are crucial for the survival and pathogenicity of C. albicans. The impact of P3 on ERG11 and ERG3 is more effective than that of Fluconazole. Molecular docking studies revealed strong binding of P3 to various isoforms of lanosterol 14-α-demethylase, a key enzyme in ergosterol synthesis. Furthermore, molecular dynamic simulations validated the stability of the most promising docking complex. Overall, our findings underscore P3's potential as a leading candidate for the development of innovative antifungal therapies, warranting further investigation and optimization.

The Real-World Effectiveness of Antifungals in People with Cystic Fibrosis and Aspergillus-Positive Cultures.

The pathogenicity of Aspergillus in the cystic fibrosis (CF) airway is debated, leading to unclear clinical benefit of antifungal therapy for Aspergillus infection. To determine the real-world effectiveness of antifungal use in people with CF (PwCF) with Aspergillus species in the United States. We conducted a retrospective cohort study evaluating the association of antifungal use and respiratory outcomes in PwCF and Aspergillus positive cultures using the Cystic Fibrosis Foundation patient registry. Marginal structural models using inverse-probability treatment weighted estimators were used to test if antifungal exposure was associated with forced expiratory volume in one second percent predicted (FEV1pp) and pulmonary exacerbation rate, while controlling for fixed and time-varying confounders. We conducted sensitivity analyses on individuals with persistent Aspergillus and without concomitant allergic bronchopulmonary aspergillosis (ABPA). A total of 14,754 individuals with Aspergillus positive cultures between 2006 and 2019 were identified. Antifungals were prescribed to 3,575 (24.2%) unique PwCF during the study period. Antifungal use was not associated with FEV1pp (adjusted estimate -0.96 percentage points, 95% CI -2.21,0.29). Antifungal use was associated with 29% increased rate of pulmonary exacerbations requiring intravenous (IV) antibiotics (adjusted IRR=1.29, 95% CI 1.22, 1.37). In sensitivity analyses limited to individuals without ABPA< antifungals were associated with 1.88 lower FEV1pp (95% CI -3.35, -0.41) and an increased rate of pulmonary exacerbations (adjusted IRR= 1.30, 95% CI 1.21,1.40). Whereas, in patients with persistent Aspergillus and persistent Aspergillus without concomitant ABPA, antifungals were not associated with FEV1pp. Antifungal therapy in PwCF and Aspergillus positive cultures was not associated with improvements in FEV>1pp. While antifungal therapy was associated with increased risk for pulmonary exacerbations, this could reflect confounding by severity of disease. Randomized clinical trials examining the clinical efficacy of antifungals in Aspergillus infections are warranted.

Antifungal efficacy of photodynamic therapy on Cryptococcus and Candida species is enhanced by Streptomyces spp. extracts in vitro.

The research on actinobacteria isolated from traditional medicinal plants is limited. Here, four new Streptomyces isolates (Ha1, Pp1, UzK and UzM) were obtained from the rhizospheres of Helianthus annuus, Pongamia pinnata and Ziziphus mauritiana, frequently utilized in Indian traditional medicine. The Streptomyces isolates aqueous extracts were studied alone against the growth of the Cryptococcus neoformans H99 reference strain, the fluconazole-tolerant T1-5796 and 89-610 strains, three histone deacetylase (HDAC) genes mutant strains, C. gattii NIH198, Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis to determine minimum inhibitory concentration (MIC). Next, the extracts were employed in combination with aluminium-phthalocyanine chloride nanoemulsion-mediated photodynamic therapy to evaluate a possible interaction. We demonstrated that the C. neoformans T1-5796 fluconazole-tolerant strain was more severely inhibited by the Pp1 isolate extract (MIC: 6mg mL-1) than H99, which was not inhibited. Growth inhibition of the HDAC null mutants was more prominent for the extract of the UzM isolate, showing inhibition at 2mg mL-1. The UzM extract was also the most effective in hindering the Candida species proliferation, with MIC values ranging from 10 to 40mg mL-1. The four Streptomyces extracts, especially UzK and UzM, significantly enhanced the antifungal effect of the photodynamic therapy. Our results indicate these Streptomyces isolates as sources of novel metabolites which could potentiate the effect of photodynamic therapy in controlling yeasts superficial infections.

Design and synthesis aldehydes-thiourea and thiazolyl hydrazine derivatives as promising antifungal agents against Monilinia fructicola.

Fungal diseases present a significant threat to global agriculture, necessitating the development of new, safe, and effective fungicides. Existing fungicides face resistance and health risks, prompting the synthesis of novel compounds. Researchers have synthesized aldehyde-based thiourea and thiazolyl hydrazine derivatives, evaluating their antifungal activities to identify impactful pesticide molecules. The results showed that most of the compounds had broad-spectrum antifungal activity against six plant pathogenic fungi and four post-harvest fungi. Notably, compound LN18 showed the best antifungal activity against Monilinia fructicola with a half-maximal effective concentration (EC50) of 0.17 μg mL-1, which was better than the commercial fungicide natamycin. A structure-activity relationship (SAR) study showed that the presence of unsaturated double bonds in the structure and the length of the carbon chain were the main factors affecting antifungal activity. The presence of unsaturated double bonds and an increase in the length of the carbon chain greatly improved inhibitory activity against the tested pathogens. The preliminary mechanism study showed that LN18 could damage the integrity of the mycelial plasma membrane, leading to leakage of intracellular nucleic acid and protein. LN18 also induced an increase in the intracellular reactive oxygen species level to exert its antifungal effects. In addition, compound LN18 had a stronger antifungal effect in vivo, and better phytotoxicity than natamycin, indicating broad application prospects in agriculture. Aldehydes-thiourea and thiazolyl hydrazine derivatives demonstrate remarkable antifungal efficacy against plant pathogenic and post-harvest fungi, offering a promising avenue for commercialization as highly efficacious, cost-effective and safe antifungal agents. © 2024 Society of Chemical Industry.

Chemical Survey and Antifungal Efficacy of Sargassum muticum's Alkaloids and Phenolic-Rich Fraction Against Airborne Toxigenic and Nosocomial Opportunistic Molds Isolates.

The Atlantic coastline of El-Jadida, Morocco, is renowned for its plentiful algae, especially brown seaweed, which is rich in active compounds known for their antifungal properties. This valuable resource offers an exciting opportunity to tackle the numerous challenges posed by invasive fungal infections, allergies, mycotoxin-related food poisoning, and drug-resistant strains. Underscoring the urgent need to explore alternative, sustainable, and environmentally friendly antifungal agents derived from algae. This study aimed to evaluate the antifungal activity of total alkaloids and phenolic-rich fractions derived from seven species of Pheophyceae: Sargassum muticum, Sargassum vulgare, Bifurcaria bifurcata, Cystoseira tamariscifolia, Cystoseira humilis, Laminaria ochroleuca, and Fucus spiralis against four fungi: airborne toxigenic isolates of Aspergillus westerdijkiae and Chaetomium globosum as well as nosocomial opportunistic isolates of Aspergillus nidulans and Scopulariopsis brevicaulis. The study also aimed to identify the most effective alga and its specific active compounds through LC-MS and GC-MS analysis. The invasive Sargassum muticum was chosen as the most potent alga in inhibiting the growth of mycelium. For the first time, the alkaloids palmatine and jatrorrhizine, along with caulerpin, have been identified. The chloroform fraction revealed the prevalence of phenolic compounds including, phenolic acids, flavonoids, and phlorotannins. The lowest minimum inhibitory concentrations (MICs), with a maximum fungal load of 108 colony-forming unit (CFU), recorded ranged from 3.12 to 6.25μg/mL by the phenolic-rich fraction against airborne toxigenic isolates, and from 100 to 200μg/mL against nosocomial opportunistic isolates by the total alkaloids. In comparison, the positive control, ketoconazole, showed higher MICs and resistance against A. nidulans. The valorization of Sargassum muticum is proposed as a green strategy to preserve the ecological balance, combat antifungal resistance, and address public health challenges.

Effects of photodynamic therapy using bisdemethoxycurcumin combined with melatonin or acetyl-melatonin on C. Albicans

The current study aims to explore the efficacy of antifungal photodynamic therapy (PDT) on C. albicans biofilms by combining photosensitizers, bisdemethoxycurcumin (BDMC), and melatonin (MLT) or acetyl-melatonin (AcO-MLT). Additionally, the relationship between different types of reactive oxygen species and PDT’s antifungal efficacy was investigated. BDMC, MLT and AcO-MLT were applied, alone and in combination, to 48-hour C. albicans biofilm cultures (n = 6/group). Blue and red LED light (250 mW/cm2 with 37.5 J/cm2 for single or 75 J/cm2 for dual photosensitizer groups) were used to irradiate BDMC groups and MLT/AcO-MLT groups, respectively. For combination groups, blue LEDs and subsequently red LEDs were used. Drop plate assays were performed at 0, 1 and 6 h post-treatment. Colony forming units (CFUs) were then counted after 48 h. Hydroxyl radicals and singlet oxygen were measured using fluorescence spectroscopy and electron spin resonance (ESR) spectroscopy. Additionally, cell cytotoxicity was tested on human oral keratinocytes. Significant CFU reductions were observed with combinations 20 µM BDMC + 20 µM AcO-MLT and 60 µM BDMC + 20 µM MLT at 0 and 1 h post-treatment, respectively. Singlet oxygen production increased with the addition of MLT/AcO-MLT and had moderate-substantial correlations with inhibition at all times. Hydroxyl radical production was not significantly different from the control. Additionally, BDMC exhibited subtle cytotoxicity on human oral keratinocytes. PDT using BDMC + MLT or AcO-MLT, with blue and red LED light, effectively inhibits C. albicans biofilm through singlet oxygen generation. Melatonin acts as a photosensitizer in PDT to inhibit fungal infection.

Ultrasound-assisted fabrication of chitosan-hydroxypropyl methylcellulose nanoemulsions loaded with thymol and cinnamaldehyde: Physicochemical properties, stability, and antifungal activity

This study investigated the influence of chitosan (CH) and hydroxypropyl methylcellulose (H), along with ultrasound power, on the physicochemical properties, antifungal activity, and stability of oil-in-water (O/W) nanoemulsions containing thymol and cinnamaldehyde in a 7:3 (v/v) ratio. Eight O/W formulations were prepared using CH, H, and a 1:1 (v/v) blend of CH and H, both with and without ultrasonication (U). Compared to untreated samples, U-treated nanoemulsions had lower droplet sizes (433–301 nm), polydispersity index (0.42–0.47), and zeta potential (−0.42–0.77 mV). The U treatment decreased L* and b* values, increased a* color attribute values, and increased apparent viscosity (0.26–2.17) at the same shear rate. After 28 days, microbiological testing of nanoemulsions treated with U showed counts below the detection limits (< 2 log CFU mL−1). The U-treated nanoemulsions exhibited stronger antifungal effects against R. stolonifer, with the NE/CH-U and NE/CH-H-U formulations demonstrating the lowest minimum inhibitory and fungicidal concentrations, measured at 0.12 and 0.24 μL/mL, respectively. On day 28, U-treated nanoemulsions demonstrated higher ionic, thermal, and physical stability than untreated samples. These findings suggest that the stability and antifungal efficacy of polysaccharide-based nanoemulsions may be improved by ultrasonic treatment. This study paves the way for innovative, highly stable nanoemulsions.

Antifungal Efficacy of Panchgavya Formulations against Rhizoctonia solani: An Incitant of Rice Sheath Blight

The main rice-grown crop was found severely affected by sheath blight in the south Gujarat region. Sheath blight of rice symptoms were noticed on leaf blades and the sheath just above the water level. The isolation was done from infected parts and purified by the hyphal tip method on PDA which was maintained at 4 oC. The seven different panchgavya formulations of five cow products such as cow urine, dung, curd, ghee, and milk that designed as PG1, PG2, PG3, PG4, PG5, PG6, and PG7. The PG against test pathogen Rhizoctonia solani in vitro condition by the poisoned food technique and that tested at 2, 4, 6, 8, and 10 percent concentrations. It was observed that panchgavya were able to suppress the growth of R. solani. Among the different formulations, PG1 was significantly effective at all concentrations as compared to other PG formulations against R. solani.

Synthesis, Characterization, Bioactivity Evaluation, and POM/DFT/Docking Analysis of Novel Thiazolidine Derivatives as Potent Anticancer and Antifungal Agents

AbstractA series of 2,2′‐(1,4‐phenylene)bis(N‐substituted phenylthiazolidine‐4‐amide) derivatives, denoted as (A3–9), were synthesized, and characterized for their potential applications against prostate cancer cells (PC3), and Candida albicans fungi. These compounds incorporate various substituents on the phenyl ring such as 4‐NO2, 3‐NO2, 4‐COCH3, 4‐H, 4‐OCH3, 4‐OCH2CH3, and 4‐Cl. The chemical structures of these derivatives were confirmed by NMR, FTIR, and mass spectroscopy. Biological assays, utilizing the MTT assay for prostate cancer cells (PC3) and the disk diffusion assay for Candida albicans fungi, were conducted to evaluate the bioactivity of these compounds. The results revealed promising cytotoxic and antifungal activities. Specifically, compounds A3 (IC50=69.74±0.96), A4 (IC50=63.64±0.950), and A9 (IC50=57.14±0.88 μg/mL) exhibited notable potency against PC3 cells, while A7 and A8 exhibited considerable antifungal efficacy against Candida albicans with MIC of 312 μg/mL. Moreover, density functional theory (DFT) simulations were used to study electronic properties and reactivity descriptors such as energy gap (Eg), ionization potential (IP), electron affinity (EA), chemical potential (μ), chemical hardness (η), global softness (σ), electronegativity (χ), and electrophilicity (ω) to gain a better understanding of the Structure‐Activity Relationship (SAR). Molecular docking analysis against DNA Gyrase and EGFR tyrosine kinase enzymes revealed strong binding interactions of the investigated molecules within their active sites, making them valuable candidates for further development as therapeutic agents against prostate cancer and fungal infections. POM analysis indicates the presence of two antifungal pharmacophore sites (O1δ−, O2δ−) and (O3δ−, O4δ−), as well as two antitumor pharmacophore sites (O1δ−, NH1δ+) and (O4δ−, NH2δ+).

Electrically-driven drug delivery into deep cutaneous tissue by conductive microneedles for fungal infection eradication and protective immunity

Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality. However, the management of deep cutaneous fungal infection is challenging and yet overlooked by traditional treatments, which only offer limited drug availability within deep tissue. In this study, we have developed an electrically stimulated microneedle patch to deliver miconazole into the subcutaneous layer. We tested its antifungal efficacy using in vitro and ex vivo models that mimic fungal infection. Moreover, we confirmed its anti-fungal and wound-healing effects in a murine subcutaneous fungal infection model. Furthermore, our findings also showed that the combination of miconazole and applied current synergistically stimulated the nociceptive sensory nerves, thereby activating protective cutaneous immunity mediated by dermal dendritic and γδ-T cells. Collectively, this study provides a new strategy for minimally invasive delivery of therapeutic agents and the modulation of the neuro-immune axis in deep tissue.

Comparative analysis of antifungal properties in medicinal plant extracts for sustainable agriculture

The escalating environmental repercussions of pesticide use in pest and disease management underscore the urgency for alternative strategies. One promising avenue involves harnessing natural antifungal properties present in plant extracts. This study aimed to assess the antifungal efficacy of aqueous and ethanolic extracts from five medicinal plants, viz., C. sativa L., S. moorcraftiana L., S. nigrum L., F. vesca L., and R. pseudoacacia, which were screened for their antifungal activity against various soil-borne fungi, viz., A. niger, A. flavus, A. terreus, R. stolonifer, M. mucedo, F. oxysporum, A. alternata, P. notatum, C. cladosporioides, and C. lunata. Phytochemical analysis exhibited the presence of phenols, alkaloids, tannins, flavonoids, quinines, and terpenoids. Results revealed potent antifungal activity across all tested fungi, significantly inhibiting mycelial growth compared to control. S. nigrum and C. sativa extracts exhibited the highest efficacy against multiple fungal pathogens. The inhibition in mycelial growth in ethanolic and aqueous plant extracts of C. sativa against A. niger varies between 3.00 mm to 6.00 mm and 4.00 mm–6.33 mm, against A. flavus 3.33 mm–11.66 mm and 4 mm–12.66 mm, A. terreus (3.00 mm–6.00 mm and 3.66 mm–7.00 mm), R. stolonifer (3.00 mm–5.33 and 3.66 mm–6.33 mm), M. mucedo (8.33 mm–17.66 mm and 9.66 mm–18.66 mm), F. oxysporum (6.66 mm–12.33 mm and 7.33 mm–13.33 mm), A. alternata (4.66 mm–11.33 mm and 5.33 mm–14.00 mm), P. notatum (9.33 mm–23.00 mm and 9.66 mm–24.33 mm), C. cladosporioides (4.33 mm–8.66 mm and 5.33 mm–9.66 mm), and C. lunata (14.00 mm–20.33 mm and 17.00 mm–21.33 mm) in different concentrations of plant extracts respectively. Likewise, the inhibition in mycelial growth in ethanolic and aqueous plant extracts of S. nigrum against A. niger at different concentrations varies between 8.00 mm to 17.66 mm and 9.00 mm–18.66 mm, A. flavus (8.33 mm–12.66 mm and 9 mm–14 mm), A. terreus (2.33 mm–5.66mm and 3 mm–7 mm), R. stolonifer (13.33 mm–20.33 mm and 17.66 mm–24.66 mm), M. mucedo (10.66 mm–12.00 mm and 11.66 mm–13.00 mm), F. oxysporum (15.66 mm–22.33 and 18.00 mm–24.00 mm), A. alternata (10.66 mm–13.00 mm and 11.66 mm–14.00 mm), P. notatum (5.33 mm–13.33 mm and 6.33 mm–18.66 mm, C. cladosporioides (3.33 mm–7.66 mm and 4.00 mm–8.00 mm), and C. lunata (3.66 mm–6.33 mm and 4.66 mm–6.66 mm), respectively. These findings suggest that these plant extracts have the potential to be natural fungicides, providing promising alternatives for disease management in agriculture.

Antifungal activity of 2-chloro-5-trifluoromethoxybenzeneboronic acid and inhibitory mechanisms on Geotrichum candidum from sour rot Xiaozhou mustard root tuber

Xiaozhou mustard (Brassica napiformis) root tuber, a traditional fermented vegetable, has a long history in Rongan County, Guangxi Province. However, the frequent occurrence of root tuber sour rot by Geotrichum candidum (G. candidum) has seriously reduced Xiaozhou mustard production and quality in recent years. The objective of the present study is to investigate the antifungal efficacy of 2-chloro-5-trifluoromethoxybenzeneboronic acid (Cl-F-BBA) against G. candidum and its possible mechanisms. The results revealed that a concentration of 0.25 mg/mL Cl-F-BBA completely halted mycelial growth and spore germination. Furthermore, a slightly lower concentration of 0.20 mg/mL was sufficient to compromise the integrity of the plasma membrane in mycelia and mitochondria, leading to a reduction in respiratory rate, activities of malate dehydrogenase (MDH), and succinate dehydrogenase (SDH), ATP content, and energy charge. This concentration also significantly disordered antioxidant metabolism, resulting in the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), and caused intracellular leakage in mycelia. In vivo experiments further demonstrated that Xiaozhou mustard root tubers treated with Cl-F-BBA exhibited markedly lower decay rates and lesion diameters compared to the control group. In summary, Cl-F-BBA presents a promising solution for controlling root tuber sour rot in Xiaozhou mustard caused by G. candidum.

Synthesis, Characterization, DFT Calculations, Antimicrobial Activity, Molecular Docking, and ADMET Study of New Pyrazole-Carboxamide Derivatives

An efficient one-step synthesis of carboxamides from pyrazole acid was achieved using thionyl chloride as an activating agent. Thirteen new pyrazole carboxamide derivatives were synthesized and characterized through spectroscopic and spectrometric techniques. These compounds were evaluated for antifungal activity against Candida albicans, Aspergillus brasiliensis, and Saccharomyces cerevisiae. Notably, compounds R5, R11, and R13 showed significant antifungal efficacy, while none exhibited antibacterial activity against Escherichia coli. To further our understanding, a computational DFT analysis revealed crucial information about the structure, electronic proprieties, and reactivity of these materials. The experimental results were supported by molecular docking analysis, reinforcing the validity of the results. Extending our exploration, an analysis of the pharmacokinetic properties and toxicity by ADMET profiling confirmed the safe use of these newly synthesized compounds, paving the way for promising applications in the medical field.

Enhanced Antifungal Efficacy of Validamycin A Co-Administered with Bacillus velezensis TCS001 against Camellia anthracnose

Anthracnose, a fungal disease harming fruit trees and crops, poses a threat to agriculture. Traditional chemical pesticides face issues like environmental pollution and resistance. A strategy combining low-toxicity chemicals with biopesticides is proposed to enhance disease control while reducing chemical use. Our study found that mixing validamycin A (VMA) and Bacillus velezensis TCS001 effectively controlled anthracnose in Camellia oleifera. The combination increased antifungal efficacy by 65.62% over VMA alone and 18.83% over TCS001 alone. It caused pathogen deformities and loss of pathogenicity. Transcriptomic analysis revealed that the mix affected the pathogen’s metabolism and redox processes, particularly impacting cellular membrane functions and inducing apoptosis via glycolysis/gluconeogenesis. In vivo tests showed the treatment activated C. oleifera’s disease resistance, with a 161.72% increase in polyphenol oxidase concentration in treated plants. This research offers insights into VMA and TCS001’s mechanisms against anthracnose, supporting sustainable forestry and national edible oil security.

Antifungal Activity of Tea Tree (Melaleuca alternifolia Cheel) Essential Oils against the Main Onychomycosis-Causing Dermatophytes.

Onychomycosis is a common fungal infection that affects the nails and accounts for approximately 50% of all nail diseases. The main pathogens involved include dermatophytes, such as Trichophyton rubrum, members of the T. mentagrophytes complex, and emerging pathogens in this infection, T. schoenleinii and T. tonsurans. Tea tree (Melaleuca alternifolia Cheel) essential oil (EO) has been proposed as a promising natural alternative to traditional treatments due to its antimicrobial properties. Among its more than 100 compounds, terpinen-4-ol is one of the main contributors to the antifungal action of this EO. To determine the antifungal activity of tea tree EO against dermatophytes, we designed an in vitro study using EUCAST-AFST protocols to obtain the values of MIC (minimum inhibitory concentration) and MFC (minimum fungicidal concentration) of several commercial M. alternifolia Cheel EOs against three species of dermatophytes isolated from clinical samples with suspected toenail onychomycosis. The results showed that the microorganism most sensitive to the action of the EO was T. rubrum, which had an MIC value more than 13 times lower than the value obtained for T. schoenleinii (0.4% v/v), the most resistant isolate. No differences in antifungal activity were observed by the analysed EOs or between the MIC and MFC values. These in vitro results suggest that tea tree EO is a viable option for the alternative treatment of onychomycosis, although clinical studies are needed to confirm the long-term antifungal activity, safety and efficacy of the oils studied in a clinical context.

Reactive oxygen species-inducing itraconazole and its anti-biofilm activity against resistant Candida parapsilosis sensu lato biofilm cells isolated from patients with recalcitrant onychomycosis.

Candida parapsilosis was introduced as the second most responsible for nail involvement. The colonization of biotic and abiotic surfaces by Candida spp.can result in the formation of biofilms, which possess a high level of resistance to typical antifungal agents. Since Candida spp. can produce biofilm mass on the surface of the nails, dermatologists should consider appropriate antifungals to eliminate both the planktonic and biofilm cells. The aim of this research was to determine the antifungal efficacy of itraconazole against C. parapsilosis sensu lato biofilm formations, in addition to its static effects. Ten C. parapsilosis sensu lato isolates were enrolled in this study. The use of itraconazole results in the accumulation of reactive oxygen species (ROS) during treatment. In order to verify the correlation between ROS and itraconazole-induced cell death, the viability of cells was analyzed by administering the ROS scavenger Ascorbic acid. The apoptotic features of itraconazole were analyzed using the Annexin V-FITC method. Based on current data, it was found that the generation of intracellular stresses by itraconazole is not observed in cells upon ROS inhibition, emphasizing the importance of intracellular ROS in the apoptotic mechanism of itraconazole. Targeting the oxidative defense system is a powerful point to use ROS-inducing antifungals as a superior choice for more effective therapies in case of recalcitrant onychomycosis.