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UNLABELLED: Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

Background: The emergence of tolerance to antifungal agents in Candida albicans complicates the treatment of fungal infections. Understanding the mechanisms underlying this tolerance is crucial for developing effective therapeutic strategies. Objective: This study aims to elucidate the genetic and molecular basis of ketoconazole tolerance in C. albicans, focusing on the roles of chromosomal aneuploidy, Hsp90, and calcineurin. Methods: The wild-type C. albicans strain SC5314 was exposed to increasing concentrations of ketoconazole (0.015-32 µg/mL) to select for tolerant adaptors. Disk diffusion and spot assays were used to assess tolerance. Wholegenome sequencing identified chromosomal changes in the adaptors. The roles of Hsp90 and calcineurin in maintaining and developing ketoconazole tolerance were investigated using specific inhibitors and knockout strains. Results: Adaptors exhibited tolerance to ketoconazole concentrations up to 16 µg/mL, a significant increase from the parent strain's inhibition at 0.015 µg/mL. All tolerant adaptors showed amplification of chromosome R, with 29 adaptors having trisomy and one having tetrasomy. This aneuploidy was unstable, reverting to euploidy and losing tolerance in drug-free conditions. Both Hsp90 and calcineurin were essential for maintaining and developing ketoconazole tolerance. Inhibition of these proteins resulted in loss of tolerance. The efflux gene CDR1 was not required for the development of tolerance. Chromosome R trisomy and tetrasomy induce cross-tolerance to other azole antifungal agents, including clotrimazole and miconazole, but not to other antifungal classes, such as echinocandins and pyrimidines, exemplified by caspofungin and 5-flucytosine. Conclusion: Ketoconazole tolerance in C. albicans is mediated by chromosomal aneuploidy, specifically chromosome R amplification, and requires Hsp90 and calcineurin. These findings highlight potential targets for therapeutic intervention to combat antifungal tolerance and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

• The lectin WSMoL inhibited the growth of C. neoformans B3501 and C. gattii R26. • Lectin treatment resulted in damage to the integrity of the lysosomes of yeast cells. • WSMoL also caused reduction of the mitochondrial membrane potential of C. neoformans B3501. • WSMoL inhibited biofilm formation by C. neoformans B3501. Moringa oleifera seeds contain a water-soluble lectin (WSMoL) that exerts antimicrobial effects against bacteria and Candida yeasts. In this study, we evaluated the activity of WSMoL against Cryptococcus neoformans (B3501 and H99) and Cryptococcus gattii (R265). Antifungal activity was evaluated by determining the minimum inhibitory concentration (MIC). Changes in the mitochondrial membrane potential of cells exposed to lectin were assessed using the fluorescent probe rhodamine 123. Moreover, the effect of WSMoL on the lysosomal membrane integrity was assessed via acridine orange staining. WSMoL exhibited an MIC of 6.25 µg/mL for all strains but did not exhibit any fungicidal activity. WSMoL caused lysosomal damage in C. neoformans B3501 and C. gattii R265 cells and reduced the mitochondrial membrane potential in C. neoformans B3501. Additionally, at concentrations of 25–400 µg/mL, WSMoL inhibited biofilm formation by C. neoformans B3501, the only isolate capable of producing biofilms. In conclusion, WSMoL exhibits antifungal activity, causing lysosomal and mitochondrial damage and inhibiting growth and biofilm formation in Cryptococcus yeasts. [ABSTRACT FROM AUTHOR]

Over the last few years, varieties of fungal infections have created a serious threat to human populations worldwide. Fungi are prone to develop infections mainly in immune-compromised individuals, like patients suffering from HIV/AIDS, diabetes, and hematological disorders. Alarmingly, this threat is continuously increasing with the use of the long-term therapeutic and prophylactic use of antifungal agents that have promoted the emergence of multi-drug resistant fungi. Therefore, there is a need to use alternative antifungal agents that will act even against multi-drug-resistant fungi. Among all nanoparticles zinc oxide nanoparticles (ZnO NPs) received much more attention worldwide due to their unique properties like diverse morphology, large surface area to volume ratio, biocompatibility, broad-spectrum antibacterial, antifungal activities, less sensitivity for the development of resistance towards micro-organisms and stay non-hazardous in the environment. This review aims to discuss the multiple drug resistance in fungi, the general properties of ZnO, their synthesis methods, their antifungal applications, their antifungal mechanism, and the nanotoxicity of ZnO. This review will offer a door for the use of ZnO NP-based materials as an alternative approach for treating multi-drug resistant fungal infections. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effects of chloroquine alone and in combination with traditional antifungal agents on the Candida albicans biofilms and its drug resistance. Methods This study used standard strains of Candida albicans, and drug-resistant strains of Candida albicans. The inhibitory effects of chloroquine alone and in combination with antifungal drugs on biofilms of Candida albicans were detected by XTT reduction method and chessboard dilution method respectively. The morphological characteristics of biofilms were observed under scanning electron microscopy. Results Chloroquine at the concentration of 50 μmol/L or above showed a direct inhibitory effect and increased with concentration. Chloroquine combined with amphotericin B had a synergistic inhibitory effect. Results of the time-killing curve showed that the growth trends of biofilms treated with chloroquine alone and combined with amphotericin B varied in different time periods during the experimental culture. Morphological observation also revealed that chloroquine alone and in combination with amphotericin B could reduce the ability of Candida albicans to form hyphae and biofilms. Conclusion Chloroquine has an inhibitory effect on Candida albicans biofilms and can reduce its drug resistance. Furthermore, chloroquine shows a synergistic anti-fungal effect when combined with amphotericin B.

The emergence of Candida auris as a multidrug-resistant fungal pathogen represents a significant global health challenge, especially given the growing issue of antifungal drug resistance. This review aims to illuminate the potential of essential oils (EOs), which are volatile plant secretions containing complex mixtures of chemicals, as alternative antifungal agents to combat C. auris, thus combining traditional insights with contemporary scientific findings to address this critical health issue. A systematic literature review was conducted using the PubMed, Scopus, and Web of Science databases from 2019 to 2024, and using the Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol to identify relevant studies on the antifungal efficacy of EOs or their components against C. auris. Of the 90 articles identified, 16 were selected for detailed review. The findings highlight the diverse mechanisms of action of EOs and their components, such as disrupting fungal cell membranes, inducing the production of reactive oxygen species (ROS), and impeding biofilm formation, suggesting that some of them may be as effective as, or better than, traditional antifungal drugs while potentially limiting the development of resistance. However, issues such as variability in the composition of EOs and a paucity of clinical trials have been identified as significant obstacles. In conclusion, EOs and their active ingredients are emerging as viable candidates for creating effective treatments for C. auris, underscoring their importance as alternative or complementary antifungal agents in the face of increasing drug resistance. The call for future research underscores the need for clinical trials and standardization to unlock the full antifungal potential of EOs against C. auris. [ABSTRACT FROM AUTHOR]

Background: Histoplasma capsulatum is the causative agent of histoplasmosis, a dimorphic fungal disease. The study aimed at determining prevalence and susceptibility pattern of Histoplasma capsulatum among patients with pulmonary infection in Northern Nigeria. Material and Methods: This is a cross sectional and hospital-based study. Samples were collected from patients and questionnaires were administered. Three hundred and twenty-two sputum samples were collected and analysed with standard microbiological methods. The use of lactophenol cotton blue dye, revealed the presence of yeast like cells. Varieties differentiation was done by urease test. Sociodemographic and risk factors associated with histoplasmosis were determined by administering questionnaires to participants. Antifungal E-test strips were used to determine the susceptibility and data analysed by Statistical Package for Social Sciences version 20 at 5% significance level. Results: Histoplasma var. duboisii was isolated with 18(5.59 %) prevalence. Geriatric age (12.5 %), had the highest prevalence among the age groups in the study. Males (8.07 %), having high prevalence than females (3.10 %). The married and Civil servants had 6.25 %, and 8.69 % prevalence respectively and statistically associated with histoplasmosis. The immunocompromised and traders among the risk factors considered in the study, has an odd ratio of 1.026 and 1.060. Amphotericin B was most effective in this study. Conclusion: Histoplasmosis mimics tuberculosis in clinical presentations, hence, should be diagnosed alongside tuberculosis infection before commencement of therapy, awareness campaign, public policy should be made by the government on its presence and how to tackle the disease alongside AIDS and Tuberculosis. [ABSTRACT FROM AUTHOR]

(1) Background: Although Candida albicans accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2) Methods: A biofilm formation assay with RPMI1640 medium was performed with Liriope muscari extract. A combination antifungal assay, dimorphic transition assay, and adhesion assay were performed under the biofilm formation condition to determine the anti-biofilm formation effect. qRT-PCR analysis was accomplished to confirm changes in gene expression; (3) Results: L. muscari extract significantly reduces biofilm formation by 51.65% at 1.56 μg/mL use and therefore increases susceptibility to miconazole. L. muscari extract also inhibited the dimorphic transition of Candida; nearly 50% of the transition was inhibited when 1.56 μg/mL of the extract was treated. The extract of L. muscari inhibited the expression of genes related to hyphal development and extracellular matrix of 34.4% and 36.0%, respectively, as well as genes within the Ras1-cAMP-PKA, Cph2-Tec1, and MAP kinase signaling pathways of 25.58%, 7.1% and 15.8%, respectively, at 1.56 μg/mL of L. muscari extract treatment; (4) Conclusions: L. muscari extract significantly reduced Candida biofilm formation, which lead to induced antifungal susceptibility to miconazole. It suggests that L. muscari extract is a promising anti-biofilm candidate of Candida albicans since the biofilm formation of Candida albicans is an excellent target for candidiasis regulation. [ABSTRACT FROM AUTHOR]

Currently, fungal susceptibility measurement methods in Japan are based on CLSI standards. However, since the CLSI document is frequently revised, discrepancies may arise in the measurement results if tests are conducted without awareness of the revised contents. We checked the history and latest editions of M27, a document on yeast fungi, and M38, a document on filamentous fungi. Regarding M27, we identified important changes regarding the latest measurement methods. We also identified various problems regarding susceptibility measurement reagents. Here. we discuss these changes and problems. [ABSTRACT FROM AUTHOR]

Cyclopentadienyl half‐sandwich complexes of cobalt and iron with metal–iodide bonds were reported to efficiently inhibit the growth of phytopathogenic fungi. With the aim of investigating the structure/activity relationships, further in vitro experiments were carried out. Cyclic voltammetric characterization, chemical stability, and antiradical activity were performed in two solvents: dimethyl sulfoxide and acetone. The iodide ion removal from the complex appears to be the key point of antifungal activity. Moreover, a preliminary cell viability test on human keratinocytes was also assessed in order to verify the nontoxic effect of tested compounds. The cytotoxicity for all the complexes was comparable with that shown by povidone iodide, a common antifungal agent recognized as safe (IC50 > 300 mM). Furthermore, the work proposes an additional roadmap (sequence of experiments) at the initial antifungal activity tests, which improves insight into their mechanism of action. [ABSTRACT FROM AUTHOR]

The utilization of Cold Plasma (CP) technology for decontamination and disinfection has garnered considerable attention across diverse industries. This study aims to investigate the interaction between pH and electrical conductivity (EC) (μS/cm) in Cold Plasma-Activated Water (CPAW) enriched with metal cations and its potential as an antifungal agent against two Penicillium (P.) mold strains. The investigation focuses on elucidating the augmented chemical interactions induced by plasma between radicals, charged particles, and microorganisms' cell membranes within an aqueous environment. Our findings demonstrate a positive correlation between the inactivation potential of CPAW (operating at 10 kV voltage, 2.5 kHz high frequency, and 500 mA current intensity) and pH and EC(μS/cm) values. Notably, the relative chemical reactivity and solubility of calcium oxide emerge as significant factors, highlighting the pronounced link between P. Italicum and Plasma-Activated Water containing Copper cations (CPAW + Cu2+) (p

ABSTRACT Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis.IMPORTANCEInvasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

ABSTRACTBackground Antifungal resistance is a major problem, commonly caused by drug-efflux pump overexpression. To evaluate if chitosan could be effective in drug-resistant Candida infections, we investigated the effects of efflux pumps on antifungal activity of chitosan.Materials and Methods The minimal fungicidal concentration (MFC) of oligomer (7–9 kD) and polymer (900–1,000 kD) chitosan against Saccharomyces cerevisiae and Candida albicans were evaluated by broth and agar dilution methods. The MFCs of S. cerevisiae with single deletion of efflux pump genes, with deletion of seven efflux pumps (AD∆), and AD∆ overexpressing C. albicans efflux pump genes (CDR1, CDR2 and MDR1) were determined. C. albicans with homozygous deletions of CDR1 and of CDR2 were generated using CRISPR-Cas9 system and tested for chitosan susceptibility.Results While deleting any individual efflux pump genes had no effect on chitosan susceptibility, simultaneous deletion of multiple pumps (in AD∆) increased sensitivity to both types of chitosan. Interestingly, the overexpression of CDR1, CDR2 or MDR1 in AD∆ barely affected its sensitivity. Moreover, C. albicans with homozygous deletions of CDR1 and/or CDR2 showed similar sensitivity to wildtype.Conclusion Thus, C. albicans susceptibility to chitosan was not affected by drug-efflux pumps. Chitosan may be a promising antifungal agent against pump-overexpressing azole-resistant C. albicans.

Hyphal pellet formation by Aspergillus species in liquid cultures is one of the main obstacles to high-throughput anti- Aspergillus reagent screening. We previously constructed a hyphal dispersion mutant of Aspergillus fumigatus by disrupting the genes encoding the primary cell wall α-1,3-glucan synthase Ags1 and putative galactosaminogalactan synthase Gtb3 (Δ ags1 Δ gtb3). Mycelial growth of the mutant in liquid cultures monitored by optical density was reproducible, and the dose-response of hyphal growth to antifungal agents has been quantified by optical density. However, Δ ags1 Δ gtb3 still forms hyphal pellets in some rich growth media. Here, we constructed a disruptant lacking all three α-1,3-glucan synthases and galactosaminogalactan synthase (Δ ags1 Δ ags2 Δ ags3 Δ gtb3), and confirmed that its hyphae were dispersed in all the media tested. We established an automatic method to monitor hyphal growth of the mutant in a 24-well plate shaken with a real-time plate reader. Dose-dependent growth suppression and unique growth responses to antifungal agents (voriconazole, amphotericin B, and micafungin) were clearly observed. A 96-well plate was also found to be useful for the evaluation of mycelial growth by optical density. Our method is potentially applicable to high-throughput screening for anti- Aspergillus agents. [ABSTRACT FROM AUTHOR]

SB‐2 cationic resin has been employed as an unexpected and reusable heterogeneous organocatalyst in multicomponents reaction for the synthesis of the α‐aminophosphonates derivatives that act as antifungal agents, this reaction proceeds under eco‐friendly and simple procedure by condensation in one pot of substituted aromatic aldehydes, anilines and diethylphosphite. Excellent isolated product yields are obtained (up to 70 %) for (4 a–o) within shorter reaction times in solvent‐free condition. The synthesized compounds were determined by spectroscopic analyses such as: NMR (1H, 13C and 31P), IR and HRMS.Molecular geometries, electronic properties, stability and reactivity such as: HOMO/LUMO, ΔEGAP ${{{\rm \Delta }{\rm E}}_{{\rm G}{\rm A}{\rm P}}}$ , dipole moment (6.1308

With the emergence of the human pathogen Candida auris as a threat to human health, there is a strong demand to identify effective medicines to prevent the harm caused by such drug‐tolerant human fungi. Herein, a series of 33 new derivatives of bensulfuron methyl (BSM) were synthesized and characterized by 1H NMR, 13C NMR, and HRMS. Among the target compounds, 8a possessed the best Ki value of 1.015 μM against C. auris acetohydroxyacid synthase (CauAHAS) and an MIC value of 6.25 μM against CBS10913, a clinically isolated strain of C. auris. Taken together the structures of BSM and the synthesized compounds, it was found that methoxy groups at both meta‐position of pyrimidine ring are likely to provide desirable antifungal activities. Quantum calculations and molecular dockings were performed to understand the structure–activity relationships. The present study has hence provided some interesting clues for the discovery of novel antibiotics with this distinct mode of action. [ABSTRACT FROM AUTHOR]

Previously, the protective role of the S-layer protein 2 (Slp2) of the vaginal Lactobacillus crispatus 2029 (LC2029) strain against foodborne pathogens Campylobacter jejuni, Salmonella enterica serovar Enteritidis, and Escherichia coli O157:H was demonstrated. We demonstrate the new roles of the Slp2-positive LC2029 strain and soluble Slp2 against C. albicans infections. We show that LC2029 bacteria can adhere to the surface of the cervical epithelial HeLa cells, prevent their contact with C. albicans, and block yeast transition to a pathogenic hyphal form. Surface-bound Slp2 provides the ability for LC2029 to co-aggregate with various C. albicans strains, including clinical isolates. C. albicans-induced necrotizing epithelial damage is reduced by colonization with the Slp2-positive LC2029 strain. Slp2 inhibits the adhesion of various strains of C. albicans to different human epithelial cells, blocks yeast transition to a pathogenic hyphal form, and prevents the colonization and pathogenic infiltration of mucosal barriers. Only Slp2 and LC2029 bacteria stimulate the production of protective human β-defensin 3 in various epithelial cells. These findings support the anti-Candida albicans potential of the probiotic LC2029 strain and Slp2 and form the basis for further research on their ability to prevent and manage invasive Candida infections. [ABSTRACT FROM AUTHOR]

Since the catalyst's surface was the major active location, the inner structure's contribution to catalytic activity was typically overlooked. Here, ZnO–Co 3 O 4−v nanozymes with several surfaces and bulk oxygen vacancies were created. The O atoms of H 2 O 2 moved inward to preferentially fill the oxygen vacancies in the interior and form new "lattice oxygen" by the X-ray photoelectron spectroscopy depth analysis and X-ray absorption fine structure. The internal Co2+ continually transferred electrons to the surface for a continuous catalytic reaction, which generated a significant amount of reactive oxygen species. Inner and outer double-layer electron cycles accompanied this process. A three-dimensional model of ZnO–Co 3 O 4−v was constructed using virtual reality interactive modelling technology to illustrate nanozyme catalysis. Moreover, the bactericidal rate of ZnO–Co 3 O 4−v for Methionine-resistant Staphylococcus aureus and Multiple drug resistant Escherichia coli was as high as 99%. ZnO–Co 3 O 4−v was biocompatible and might be utilized to heal wounds following Methionine-resistant Staphylococcus aureus infection. This work offered a new idea for nanozymes to replace of conventional antibacterial medications. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (Ag-NPs) have emerged as potential antifungal agents due to their exceptional properties. These nanoparticles can be synthesised in the laboratory by using green synthetic methods. Hence, in the present study dark brown colour Ag-NPs have been synthesized from 0.01 mM AgNO3 using Azadirachta indica leaf extract as a reducing agent and characterised via different spectroscopic and microscopic techniques. The average particle sizes of the synthesized Ag-NPs are found to be 36 nm and all the particles are mostly spherical in shape. These biosynthesized Ag-NPs effectively have mitigated the mycelial growth of F. oxysporum and F. moniliforme. However, the inhibition has been found better for F. oxysporum as compared to F. moniliforme. At 500 ppm concentration of Ag-NPs, the reductions in mycelial growth have been found to be 100 and 80% for F. oxysporum and F. moniliforme, respectively. So, it can be concluded from the study that Ag-NPs prepared from A. indica leaf extracts could be explored for developing fungicidal formulations. [ABSTRACT FROM AUTHOR]

Background and Aim: Considering the increase of dermatophytosis trough the Iran and world as well, especially ringworm of the body and groin due to terbinafine-resistant species and the high speed of disease transmission, in order to choose the appropriate treatment, considering the time required for the treatment of the disease and early detection of resistant cases treatment is required. The present study was conducted to determine the antifungal sensitivity of Trichophyton rubrum, Microsporum canis and Epidermophyton flucosum strains to common antifungal drugs. Methods: Antifungal sensitivity test (broth microdilution) was performed for 20 specimens obtained from patients according to CLSI (Clinical and Laboratory Standard Institute) M38-3rd ED protocol, for terbinafine, itraconazole and voriconazole. Results: According to the antifungal susceptibility test results, 5 patients were resistant to terbinafine and showed a minimum inhibitory concentration more than 2, 3 patients were tolerant to terbinafine and showed a minimum inhibitory concentration between 0.5 and 1. Based on the results of the antifungal susceptibility test, 7 patients were tolerant to itraconazole and showed the minimum inhibitory concentration between 0.5 and 1. All isolates responded well to voriconazole. Conclusion: The results of the antifungal sensitivity test highlight the importance of mycological tests on dermatophytic skin lesions to prevent the spread of drug-resistant species. [ABSTRACT FROM AUTHOR]

Introduction: Candidiasis is a common mucocutaneous fungal infection mainly caused by Candida albicans. Infection can occur in moist areas especially in skin folds, genital cuticle, and also in oral mucosa. Oropharyngeal candidiasis will cause white plaques on oral mucosa. Nowadays resistance is developing for all diseases. In that way when there is any resistance to regular antifungal drugs, natural herbs will be an excellent option to overcome the situation. Aim: Antifungal property with minimal inhibitory concentration of Curcuma caesia (Kali haldi, black turmeric) is evaluated against C. albicans and also to find the zone of inhibition for C. caesia against C. albicans and Candida glabrata. Materials and Methods: Alcoholic extract of C. caesia was prepared. Zone of inhibition for C. albicans and C. glabrata was performed by well-diffusion method and antifungal property with minimum inhibitory concentration for C. caesia against C. albicans was done by Agar dilution method. Results: Zone of inhibition is present at about 21 mm against C. albicans and C. glabrata, Minimum inhibitory concentration is also found at 1 mg of C. caesia alcoholic extract. The results are statistically significant (P < 0.05). Conclusions: C. caesia can be used as an antifungal agent when traditional antifungal treatment is not working or in any cases of antifungal resistance. [ABSTRACT FROM AUTHOR]

Introduction: Olive (Olea europaea L.) is one of the important agricultural and medicinal tree species. This study aimed to assess the antifungal efficacy of olive leaf extract (OLE) obtained from different cultivars and during different seasons against Candida albicans strains. Methods: OLE was prepared using four olive cultivars (‘Koroneiki’, ‘Mission’, ‘Rowghani’, and ‘Zard’) obtained in two seasons (spring and autumn) from Golestan province, North of Iran. The phenolic and oleuropein contents of vegetative leaves were measured by colorimetric and HPLC techniques, respectively. The antifungal capacities of OLEs were tested by agar well diffusion and the minimal inhibitory concentration (MIC) was evaluated by micro-dilution assay. Results: The findings of our study showed that the total phenolic (27.45-88.16 mg g-1) and oleuropein (3.64-18.13 mg g-1) contents varied in leaf extracts, respectively. The highest amount was found in ‘Koroneiki’ and ‘Zard’ (spring leaves) and the lowest in ‘Mission’ cultivars (autumn leaves). The inhibition zones and MIC ranged from 1.92 to 15.41 mm and from 6.07 to 27.20 mg mL-1 based on C. albicans strains, respectively. Relationship between total phenolic content as an independent variable (X) and inhibition zones or MIC as dependent variables (Y) fitted polynomial curves. Conclusion: The present study highlighted the phytochemical and anti-candidal efficacy of OLE derived from olive cultivars or the seasons of harvested leaves against C. albicans strains. It is suggested that ‘Koroneiki’ and ‘Zard’ cultivars, especially during the spring season, could be exploited to isolate potential broad-spectrum antifungal drugs.

Abstract Background Hydroxyapatites (HAp) are widely used as medical preparations for e.g., bone replacement or teeth implants. Incorporation of various substrates into HAp structures could enhance its biological properties, like biocompatibility or antimicrobial effects. Silver ions possess high antibacterial and antifungal activity and its application as HAp dopant might increase its clinical value. Results New silicate-substituted hydroxyapatites (HAp) doped with silver ions were synthesized via hydrothermal methods. The crystal structure of HAp was investigated by using the X-ray powder diffraction. Antifungal activity of silver ion-doped HAp (with 0.7 mol%, 1 mol% and 2 mol% of dopants) was tested against the yeast-like reference and clinical strains of Candida albicans, C. glabrata, C. tropicalis, Rhodotorula rubra, R. mucilaginosa, Cryptococcus neoformans and C. gattii. Spectrophotometric method was used to evaluate antifungal effect of HAp in SD medium. It was shown that already the lowest dopant (0.7 mol% of Ag+ ions) significantly reduced fungal growth at the concentration of 100 µg/mL. Increase in the dopant content and the concentration of HAp did not cause further growth inhibition. Moreover, there were some differences at the tolerance level to Ag+ ion-doped HAp among tested strains, suggesting strain-specific activity. Conclusions Preformed studies confirm antimicrobial potential of hydroxyapatite doped with silver. New Ag+ ion-HAp material could be, after further studies, considered as medical agent with antifungal properties which lower the risk of a surgical-related infections.

The emergence of Candida auris as a multidrug-resistant fungal pathogen represents a significant global health challenge, especially given the growing issue of antifungal drug resistance. This review aims to illuminate the potential of essential oils (EOs), which are volatile plant secretions containing complex mixtures of chemicals, as alternative antifungal agents to combat C. auris, thus combining traditional insights with contemporary scientific findings to address this critical health issue. A systematic literature review was conducted using the PubMed, Scopus, and Web of Science databases from 2019 to 2024, and using the Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol to identify relevant studies on the antifungal efficacy of EOs or their components against C. auris. Of the 90 articles identified, 16 were selected for detailed review. The findings highlight the diverse mechanisms of action of EOs and their components, such as disrupting fungal cell membranes, inducing the production of reactive oxygen species (ROS), and impeding biofilm formation, suggesting that some of them may be as effective as, or better than, traditional antifungal drugs while potentially limiting the development of resistance. However, issues such as variability in the composition of EOs and a paucity of clinical trials have been identified as significant obstacles. In conclusion, EOs and their active ingredients are emerging as viable candidates for creating effective treatments for C. auris, underscoring their importance as alternative or complementary antifungal agents in the face of increasing drug resistance. The call for future research underscores the need for clinical trials and standardization to unlock the full antifungal potential of EOs against C. auris.

(1) Background: Although Candida albicans accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2) Methods: A biofilm formation assay with RPMI1640 medium was performed with Liriope muscari extract. A combination antifungal assay, dimorphic transition assay, and adhesion assay were performed under the biofilm formation condition to determine the anti-biofilm formation effect. qRT-PCR analysis was accomplished to confirm changes in gene expression; (3) Results: L. muscari extract significantly reduces biofilm formation by 51.65% at 1.56 μg/mL use and therefore increases susceptibility to miconazole. L. muscari extract also inhibited the dimorphic transition of Candida; nearly 50% of the transition was inhibited when 1.56 μg/mL of the extract was treated. The extract of L. muscari inhibited the expression of genes related to hyphal development and extracellular matrix of 34.4% and 36.0%, respectively, as well as genes within the Ras1-cAMP-PKA, Cph2-Tec1, and MAP kinase signaling pathways of 25.58%, 7.1% and 15.8%, respectively, at 1.56 μg/mL of L. muscari extract treatment; (4) Conclusions: L. muscari extract significantly reduced Candida biofilm formation, which lead to induced antifungal susceptibility to miconazole. It suggests that L. muscari extract is a promising anti-biofilm candidate of Candida albicans since the biofilm formation of Candida albicans is an excellent target for candidiasis regulation.

Background and Purpose: Candida species are opportunistic fungal pathogens that cause mild to life threatening infections in both immunocompetent and immunocompromised populations. The increasing prevalence of drug-resistant Candida species has posed a significant challenge to the management of infections in clinical settings. Therefore, this study aimed to investigate the direct antifungal and antibiofilm effect of vitamin D3 against Candida species.Materials and Methods: The antifungal activity of vitamin D3 was evaluated by broth microdilution method based on the Clinical and Laboratory Standard Institute. Prevention of biofilm formation by Candida albicans was measured using the XTT assay following exposure to different concentrations of vitamin D3. Moreover, expression of Agglutinin-like sequence gene 1 (ALS1), hyphal wall protein gene (HWP1), secreted aspartyl proteinase 6 gene (SAP6), and morphogenesis pathway regulatory gene (EFG1) were analyzed by real-time polymerase chain reaction using the comparative Ct method (ΔΔ Ct) after exposure to vitamin D3.Results: Vitamin D3 showed antifungal activity against Candida species ranging from 1-128 μg/mL. Furthermore, vitamin D3 inhibited biofilm formation in a dose-dependent manner, with IC50 of 7.5 μg/mL. Treatment with vitamin D3 resulted in significant upregulation of the EFG1, ALS1, and SAP6 genes under hypha-inducing conditions to overcome environmental challenges.Conclusion: Results of the current study demonstrated that vitamin D3 has a significant inhibitory effect on Candida growth and biofilm formation. Considering its demonstrated antifungal and antibiofilm properties, vitamin D3 holds promise as a potential agent for medical applications.

The spectrum of biological properties of s-triazine derivatives is broad and includes anti-microbial, anti-cancer, and anti-neurodegenerative activities, among others. The s-triazine molecule, due to the possibility of substituting three substituents, offers many opportunities to obtain hybrid compounds with a wide variety of activities. A group of 1,3,5 triazine derivatives containing a dipeptide, 2-ethylpiperazine, and a methoxy group as substituents was screened for their antimicrobial activity. An in vitro study was conducted on pathogenic bacteria (E. coli, S. aureus, B. subtilis, and M. luteus), yeasts (C. albicans), and filamentous fungi (A. fumigatus, A. flavus, F. solani, and P. citrinum) via microdilution in broth, and the results were compared with antibacterial (Streptomycin) and antifungal (Ketoconazole and Nystatin) antibiotics. Several s-triazine analogues have minimal inhibitory concentrations lower than the standard. To confirm the inhibitory potential of the most active compounds against gyrases E. coli and S. aureus, a bacterial gyrases inhibition assay, and molecular docking studies were performed. The most active s-triazine derivatives contained the -NH-Trp(Boc)-AlaOMe, -NH-Asp(OtBu)-AlaOMe, and -NH-PheOMe moieties in their structures. [ABSTRACT FROM AUTHOR]

There is evidence that all plants coexist with endophytes, indicating a fundamental role that is unknown. The objective was to evaluate the biotechnological potential of endophytes from Passiflora edulis f. edulis in two aspects: as a plant growth promoter and as a control for the pathogen Fusarium oxysporum. An in vitro phase was used in which the antifungal activity in a dual culture was studied, where the UNE075 and UNE004 fungi inhibited the radial growth of the pathogen by up to 67.63 % and 63.89 %, respectively. Additionally, higher inhibition percentages were seen with UNE075 (33.78 %) and UNE098 (32.32 %) because of the action of volatile organic compounds on F. oxysporum. Likewise, the production of indoleacetic acid (IAA) as a growth-promoting compound was quantified, with notable results with UNE017 (11.99 µg/mL) and UNE022 (7.59 µg/mL). The capacity of the fungi to solubilize phosphorus was determined. UNE098 generated the greatest solubilization by reducing the pH culture medium. In the in vivo phase in the greenhouse, the effect of inoculation with endophytes on the growth of P. edulis f. edulis plants was evaluated. Biomass accumulation and leaf area were determined, where UNE067 stood out because of its effect on fresh weight, total dry weight. In general, the evaluated endophytes have biotechnological potential for use in organic crop management programs and for biological control. [ABSTRACT FROM AUTHOR]

The rise in the number of fungi that resisted antifungal action is of serious concern nowadays. In this study, the potential of acid condensate (AC) produced from microwave‐assisted pyrolysis of palm kernel shell (PKS) was investigated for its antifungal properties through molecular docking evaluation. The phenolic‐rich AC was determined for its chemical compositions using the GC–MS analysis where compounds with the highest phenolics content were further evaluated (using the Autodock Tools 1.5.7) for its potential enzymes/protein binding properties. From the GC–MS analysis, catechol, guaiacol and syringol were present at highest percentages. This directly correlates with results obtained from the molecular docking works where all these ligands managed to bind (indicated by H‐bond, π‐stacking, hydrophobic interaction) with some of the amino acid at the active sites which indicate its potential to inhibit substrate binding of this enzyme. As a conclusion, this study demonstrated the potential use of AC from agricultural biomass such as PKS as a natural‐based antifungal agent that can reduce environmental and health impacts. [ABSTRACT FROM AUTHOR]

Background: Hydroxyapatites (HAp) are widely used as medical preparations for e.g., bone replacement or teeth implants. Incorporation of various substrates into HAp structures could enhance its biological properties, like biocompatibility or antimicrobial effects. Silver ions possess high antibacterial and antifungal activity and its application as HAp dopant might increase its clinical value. Results: New silicate-substituted hydroxyapatites (HAp) doped with silver ions were synthesized via hydrothermal methods. The crystal structure of HAp was investigated by using the X-ray powder diffraction. Antifungal activity of silver ion-doped HAp (with 0.7 mol%, 1 mol% and 2 mol% of dopants) was tested against the yeast-like reference and clinical strains of Candida albicans, C. glabrata, C. tropicalis, Rhodotorula rubra, R. mucilaginosa, Cryptococcus neoformans and C. gattii. Spectrophotometric method was used to evaluate antifungal effect of HAp in SD medium. It was shown that already the lowest dopant (0.7 mol% of Ag+ ions) significantly reduced fungal growth at the concentration of 100 µg/mL. Increase in the dopant content and the concentration of HAp did not cause further growth inhibition. Moreover, there were some differences at the tolerance level to Ag+ ion-doped HAp among tested strains, suggesting strain-specific activity. Conclusions: Preformed studies confirm antimicrobial potential of hydroxyapatite doped with silver. New Ag+ ion-HAp material could be, after further studies, considered as medical agent with antifungal properties which lower the risk of a surgical-related infections. [ABSTRACT FROM AUTHOR]

Background: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans, whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans-induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG). Methods: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated. Results: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans (p < 0.001) by 1.2 log10 for Hy.NLC-HG/PDT and 1.9 log10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group. Conclusions: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is an invasive fungus that causes both acute and chronic infections, especially in immunocompromised patients. Owing to the increase in the prevalence of drug-resistant pathogenic fungi and the limitations of current treatment strategies, drug repositioning has become a feasible strategy to accelerate the development of new drugs. In this study, the minimum inhibitory concentration of vitamin D3 (VD3) against C. neoformans was found to be 0.4 mg/mL by broth microdilution assay. The antifungal activities of VD3 were further verified by solid dilution assays and "time-kill" curves. The results showed that VD3 reduced fungal cell adhesion and hydrophobicity and inhibited biofilm formation at various developmental stages, as confirmed by crystal violet staining and the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Fluorescence staining of cellular components and a stress susceptibility assay indicated that VD3 compromised cell integrity. Reverse transcription quantitative PCR demonstrated that VD3 treatment upregulated the expression of fungal genes related to cell wall synthesis (i.e., CDA3, CHS3, FKS1, and AGS1). Moreover, VD3 enhanced cell membrane permeability and caused the accumulation of intracellular reactive oxygen species. Finally, VD3 significantly reduced the tissue fungal burden and prolonged the survival of Galleria mellonella larvae infected with C. neoformans. These results showed that VD3 could exert significant antifungal activities both in vitro and in vivo, demonstrating its potential application in the treatment of cryptococcal infections. [ABSTRACT FROM AUTHOR]

Abstract Background Micafungin is an echinocandin-type antifungal agent used for the clinical treatment of invasive fungal infections. It is semisynthesized from the sulfonated lipohexapeptide FR901379, a nonribosomal peptide produced by the filamentous fungus Coleophoma empetri. However, the low fermentation efficiency of FR901379 increases the cost of micafungin production and hinders its widespread clinical application. Results Here, a highly efficient FR901379-producing strain was constructed via systems metabolic engineering in C. empetri MEFC09. First, the biosynthesis pathway of FR901379 was optimized by overexpressing the rate-limiting enzymes cytochrome P450 McfF and McfH, which successfully eliminated the accumulation of unwanted byproducts and increased the production of FR901379. Then, the functions of putative self-resistance genes encoding β-1,3-glucan synthase were evaluated in vivo. The deletion of CEfks1 affected growth and resulted in more spherical cells. Additionally, the transcriptional activator McfJ for the regulation of FR901379 biosynthesis was identified and applied in metabolic engineering. Overexpressing mcfJ markedly increased the production of FR901379 from 0.3 g/L to 1.3 g/L. Finally, the engineered strain coexpressing mcfJ, mcfF, and mcfH was constructed for additive effects, and the FR901379 titer reached 4.0 g/L under fed-batch conditions in a 5 L bioreactor. Conclusions This study represents a significant improvement for the production of FR901379 and provides guidance for the establishment of efficient fungal cell factories for other echinocandins.

CONTEXT: Denture relining materials are soft and resilient materials used in the treatment of patients with denture soreness. Studies have concluded that rugged surface of the liners allows the sticking of the Candida albicans and later gives rise to a condition called denture-induced stomatitis. AIMS: The aim of this study is to evaluate and compare the antifungal efficacy and potency of denture soft liners incorporated with powder extract of Lawsonia inermis and Withania somnifera on the growth of C. albicans. MATERIALS AND METHODS: A total of 105 samples were taken in this in vitro study and was divided into three groups: To check for the antifungal activity with 35 samples each. L. inermis and W. somnifera powder extract were incorporated in soft liner at 1%, 3%, 5%, and 7% concentration and the antifungal efficacy against C. albicans was tested by calculating the diameter of inhibition zone for 1, 7, and 14 days. Statistical analysis used: Subgroup analysis was carried out using one-way analysis of variance (ANOVA) test. Pair-wise comparisons were carried out through Tukey's multiple post hoc procedures. RESULTS: When comparison of four subgroups (1%, 3%, 5%, and 7%) was done with the mean zone of antifungal efficacy at 1st day, 7th day, and 14th day time points in both the groups by one-way ANOVA, statistically significant results were obtained with P of 0.0001. CONCLUSIONS: L. inermis and W. somnifera natural herb extracts have shown to have antifungal activity against C. albicans and can be used as an alternative for the synthetic antifungal drugs.

The carriage of Candida albicans in children's oral cavities is associated with a higher risk for early childhood caries, so controlling this fungus in early life is essential for preventing caries. In a prospective cohort of 41 mothers and their children from 0 to 2 years of age, this study addressed four main objectives: (1) Evaluate in vitro the antifungal agent susceptibility of oral Candida isolates from the mother-child cohort; (2) compare Candida susceptibility between isolates from the mothers and children; (3) assess longitudinal changes in the susceptibility of the isolates collected between 0 and 2 years; and (4) detect mutations in C. albicans antifungal resistance genes. Susceptibility to antifungal medications was tested by in vitro broth microdilution and expressed as the minimal inhibitory concentration (MIC). C. albicans clinical isolates were sequenced by whole genome sequencing, and the genes related to antifungal resistance, ERG3, ERG11, CDR1, CDR2, MDR1, and FKS1, were assessed. Four Candida spp. (n = 126) were isolated: C. albicans, C. parapsilosis, C. dubliniensis, and C. lusitaniae. Caspofungin was the most active drug for oral Candida, followed by fluconazole and nystatin. Two missense mutations in the CDR2 gene were shared among C. albicans isolates resistant to nystatin. Most of the children's C. albicans isolates had MIC values similar to those from their mothers, and 70% remained stable on antifungal medications from 0 to 2 years. For caspofungin, 29% of the children's isolates showed an increase in MIC values from 0 to 2 years. Results of the longitudinal cohort indicated that clinically used oral nystatin was ineffective in reducing the carriage of C. albicans in children; novel antifungal regimens in infants are needed for better oral yeast control. [ABSTRACT FROM AUTHOR]

With increasing human awareness of food safety, the replacement of highly toxic pesticides with biocompatible antimicrobials has become a trend. This study proposes a biocontrol microneedle (BMN) to expand the application of the food-grade preservative epsilon-poly-L-lysine (ε-PL) in fruit preservatives by utilizing a dissolving microneedle system. The macromolecular polymer ε-PL not only possesses broad-spectrum antimicrobial activity but also exhibits good mechanical properties. With the addition of a small amount of polyvinyl alcohol, the mechanical strength of the ε-PL-based microneedle patch could be further improved to achieve an enhanced failure force of needles at 1.6 N/needle and induce an approximately 96% insertion rate in citrus fruit pericarps. An ex vivo insertion test revealed that the microneedle tips could be effectively inserted into the citrus fruit pericarp, rapidly dissolve within 3 min, and produce inconspicuous needle holes. Moreover, the high drug loading capacity of BMN was observed to reach approximately 1890 μg/patch, which is essential for enhancing the concentration-dependent antifungal activity of ε-PL. The drug distribution study has confirmed the feasibility of mediating the local diffusion of EPL in the pericarp through BMN. Therefore, BMN has great potential to reduce the incidence of invasive fungal infections in local areas of citrus fruit pericarp. [ABSTRACT FROM AUTHOR]

As a byproduct of bromelain extraction procedures, pineapple stem flour is underutilized. Since water glues derived from gelatinization typically have poor mold resistance, this study aims to produce flour-based value-added products, such as mold-resistant water-based adhesives. To address this issue, this study explored the use of apple cider vinegar (ACV) as a low-cost, non-toxic, commercially available antifungal agent to improve the mold resistance of adhesives. Furthermore, laurate flour was produced via a transesterification of the flour and methyl laurate using a K2CO3 catalyst. Both the unmodified flour and the functionalized flour were employed to prepare water-based adhesives. For both flour systems, adding ACV at concentrations of at least 2.0% v/v enhanced the mold resistance of the adhesives and completely inhibited the development of A. niger mycelia for up to 90 days of storage. The adhesives made from the transesterified flour exhibited a higher shear strength for the paper bonding (ca. 8%) than the unmodified ones. Additionally, the ACV additive had no negative effects on the shear strengths of the water-based adhesives. All of the flour-based adhesives developed in this study had a higher shear strength for paper substrates than two locally available commercial water glues. [ABSTRACT FROM AUTHOR]

Aim: Soft denture lining materials are susceptible to be colonized by different microorganisms, especially by Candida albicans (C. albicans), causing denture-induced stomatitis. This study was designed to evaluate the effectiveness of incorporating titanium dioxide nanoparticles (TiO2 NPs) into a soft denture liner towards reducing microbial activity. Method: A total of 40 PEMA-TiO2 nanocomposites samples were fabricated by adding 0.0 wt.% (control), 1.0 wt.%, 1.5 wt.%, and 2 wt.% TiO2 NPs to a heat cured soft denture lining material (polyethyl methacrylate, PEMA). The prepared samples were divided into four groups (n = 10) according to the content of TiO2 NPs. The uniformity of TiO2 NPS distribution within the denture liner matrix was assessed using a Scanning Electron Microscope (SEM). The viable count of C. albicans was evaluated to test the antifungal resistance of the developed composite. Results: The SEM images showed fairly homogeneous dispersion, with patches of TiO2 NPs agglomeration within the PEMA matrix and an increasing concentration of NPs with higher NP content. The particle map and EDX analysis confirmed the evidence of the TiO2 NPs. The mean viable count results for the control (0.0 wt.%) and 1.0 wt.%, 1.5 wt.%, and 2 wt.% TiO2 groups were 139.80, 12.00, 6.20, and 1.00, respectively, with a significant difference from the control group (p < 0.05). The antifungal activity also increased with the increase in the concentration of TiO2 NPs. Conclusions: The addition of TiO2 NPs into a heat-cured soft denture liner provided antifungal activity as evidenced by the reduced colonization of C. albicans. The antimicrobial activity of the liner material increased with the increased concentration of TiO2 NPS. [ABSTRACT FROM AUTHOR]

Invasive forms of aspergillosis of the nervous system are relatively rare and are usually diagnosed in immunocompromised patients. We present the case of a young female patient, treated in the last two months with corticosteroids and antifungal drug for pulmonary aspergillosis, who developed progressive paraparesis. An intramedullary abscess at the C7–D1 level was identified and the lesion was treated with a combination of surgery and antifungal therapy. Histopathologic findings of surgical specimens showed myelomalacia with Aspergillus hyphae and a peripheral rim of neutrophils. We consider that the use of multiple drugs and corticosteroids for our patient's initial community pneumonia could be the factor that transformed her into a mildly immunocompromised individual and permitted the Aspergillus spp. to disseminate through the blood and into the spinal cord. Moreover, we highlight the fact that more attention should be paid to living and working conditions of the patients, as a simple colonization of the lung with Aspergillus spp. could develop, in a short time, into an invasive disease with a high risk of mortality. [ABSTRACT FROM AUTHOR]

Background: Dentures with antimicrobial properties are desirable for preventing Candida albicans adhesion. This study was to assess the effectiveness of bioactive glass (BAG) on C. albicans adhesion, surface roughness, and hardness of denture base materials. Methods: Heat-polymerized (HP) and autopolymerized (AP) acrylic resins were used to fabricate 240 disk specimens (120/material, 60/C. albicans, 60/surface roughness and hardness). Specimens were divided into five groups (n = 10) based on the BAG concentration: 0.5, 1.5, 3, 5, and 7.5 wt% of the acrylic powder, with a control group comprised of unmodified specimens. Direct culture method was used to assess C. albicans adhesion. A profilometer and Vickers hardness test were used to measure surface roughness and hardness respectively. Analysis of variance (ANOVA) and post hoc Tukey’s test were used for data analysis (α = 0.05). Results: BAG addition significantly decreased the C. albicans count when compared with the control group (P 0.05), while the AP acrylic resins exhibited significantly higher surface roughness with BAG addition (P

Background: Micafungin is an echinocandin-type antifungal agent used for the clinical treatment of invasive fungal infections. It is semisynthesized from the sulfonated lipohexapeptide FR901379, a nonribosomal peptide produced by the filamentous fungus Coleophoma empetri. However, the low fermentation efficiency of FR901379 increases the cost of micafungin production and hinders its widespread clinical application. Results: Here, a highly efficient FR901379-producing strain was constructed via systems metabolic engineering in C. empetri MEFC09. First, the biosynthesis pathway of FR901379 was optimized by overexpressing the rate-limiting enzymes cytochrome P450 McfF and McfH, which successfully eliminated the accumulation of unwanted byproducts and increased the production of FR901379. Then, the functions of putative self-resistance genes encoding β-1,3-glucan synthase were evaluated in vivo. The deletion of CEfks1 affected growth and resulted in more spherical cells. Additionally, the transcriptional activator McfJ for the regulation of FR901379 biosynthesis was identified and applied in metabolic engineering. Overexpressing mcfJ markedly increased the production of FR901379 from 0.3 g/L to 1.3 g/L. Finally, the engineered strain coexpressing mcfJ, mcfF, and mcfH was constructed for additive effects, and the FR901379 titer reached 4.0 g/L under fed-batch conditions in a 5 L bioreactor. Conclusions: This study represents a significant improvement for the production of FR901379 and provides guidance for the establishment of efficient fungal cell factories for other echinocandins. [ABSTRACT FROM AUTHOR]

A Pharmaceutical Fungicide Or Fungistatic Used To Treat And Prevent Mycoses Such As Athlete's Foot, Ringworm, Candidiasis (Thrush), Serious Systemic Infections Such As Cryptococcal Meningitis, And Others Is Known as An Antifungal Medicine, Sometimes Known as An Antimycotic Medication. A Series Of 1,2,4 Triazole Analogs Have Been Designed Synthesized Characterized And Screened For A Wide Variety Of Therapeutically Interesting Drug Candidates Including Antifungal Agents, Anti-Inflammatory, Central Nervous System Stimulants, Antianxiety And Antimicrobial Agents. Among Screened Compound N-((4-P-Toluidine Methyl) Piperazine-1-Yl) Methyl)-4H-1,2,,4-Triazole -3-Amine Mono, Di Or Tri-Substituted Aniline Derivative Were Synthesized By Microwave Irradiation And Characterized By Proton Nuclear Magnetic Resonance (1H NMR), Infra-Red(IR), And Mass Spectroscopy (MS), And Biologically Screen For Antifungal Activity. The Novel Synthesized Derivative Triazole Show Antifungal Activity, Candida Albicans. [ABSTRACT FROM AUTHOR]