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In Candida albicans, Cdr1 pumps azole drugs out of the cells to reduce intracellular accumulation at detrimental concentrations, leading to azole-drug resistance. Milbemycin oxime, a veterinary anti-parasitic drug, strongly and specifically inhibits Cdr1. However, how Cdr1 recognizes and exports azole drugs, and how milbemycin oxime inhibits Cdr1 remain unclear. Here, we report three cryo-EM structures of Cdr1 in distinct states: the apo state (Cdr1Apo), fluconazole-bound state (Cdr1Flu), and milbemycin oxime-inhibited state (Cdr1Mil). Both the fluconazole substrate and the milbemycin oxime inhibitor are primarily recognized within the central cavity of Cdr1 through hydrophobic interactions. The fluconazole is suggested to be exported from the binding site into the environment through a lateral pathway driven by TM2, TM5, TM8 and TM11. Our findings uncover the inhibitory mechanism of milbemycin oxime, which inhibits Cdr1 through competition, hindering export, and obstructing substrate entry. These discoveries advance our understanding of Cdr1-mediated azole resistance in C. albicans and provide the foundation for the development of innovative antifungal drugs targeting Cdr1 to combat azole-drug resistance. Candida albicans Cdr1 pumps azole antifungal drugs out of the cell, driving drug resistance. Here, the authors determine the mechanism of Cdr1-mediated fluconazole resistance and milbemycin oxime inhibition, providing a foundation for future drug discovery efforts. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to develop a double antigen sandwich ELISA (DAgS-ELISA) method for more efficient, accurate, and quantitative detection of total antibodies against Candida albicans enolase1 (CaEno1) for diagnosing invasive candidiasis (IC). Methods: DAgS-ELISA was developed using recombinant CaEno1 and a monoclonal antibody as the standard. Performance evaluation included limit of detection, accuracy, and repeatability. Dynamic changes in antibody levels against CaEno1 in serum from systemic candidiasis mice were analyzed using DAgS-ELISA. Patient serum samples from IC, Candida colonization, bacterial infections, and healthy controls were analyzed with DAgS-ELISA and indirect ELISA. Results: DAgS-ELISA outperformed indirect ELISA in terms of linear range and test background. In systemic candidiasis mice, a distinctive 'double-peak' pattern in dynamic antibody levels was observed. Additionally, there was a high level of consistency in the positive rates of CaEno1 antibodies detected by both DAgS-ELISA and indirect ELISA. While the positivity rates differed among patient groups, no significant variations in antibody levels were detected among the various positive patient groups. Conclusions: DAgS-ELISA offers a reliable novel approach for IC diagnosis, enabling rapid, accurate, and quantitative detection of CaEno1 antibodies. Further validation and optimization are needed for its clinical application and effectiveness. [ABSTRACT FROM AUTHOR]

The increasing prevalence of antibiotic-resistant pathogens necessitates the development of novel antimicrobial agents. Herein, PEGylated konjac gum-supported rosin pentaerythritol nanocomposites (KG/PEG/RE PNCs) were synthesized using an environmentally friendly sonochemical method, aiming to explore their potential antibacterial and antifungal properties against a range of pathogens, including Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Aspergillus brasiliensis, and Staphylococcus aureus. An elaborate investigation into the rheological properties of these PNCs highlighted the dependence of viscosity on synthesis parameters such as RE concentration, sonication time, and KG/RE blend ratio with the Higiro model validated as a suitable mathematical model for defining the intricate relationship between experimental and resulting viscosity of PNCs. The integration of machine learning (ML), particularly polynomial regression, enabled the modeling of the complex dynamics influencing PNC viscosity, thus advancing comprehension of PNCs behavior in relation to the synthesis parameters. The modeling facilitated precise formulation to predict PNC viscosity with high accuracy, as confirmed by a mean squared error (MSE) of 3.81 and an R2 of 0.993. Moreover, the PNCs demonstrated broad-spectrum antimicrobial activity, reaching an inhibition plateau during the first week, confirming its efficacy as a versatile antibacterial and antifungal agent. Combining advanced data modeling techniques with biological assessments, this integrated approach represents a step forward in understanding and optimizing polymeric nanostructures. [ABSTRACT FROM AUTHOR]

Objective: In this work, in order to optimize the structure of histidine-containing antifungal peptides with a "linear" type of amphipathicity (LTA), we carried out the synthesis and comparative screening of the antifungal activity of a series of histidine-containing SAMPs (F2H7, F2H10, F2H13, F2H16, H10, H10F2) with a "linear" type of amphipathicity that we constructed de novo. We also aimed to study their hemolytic properties, to assess their therapeutic index, and to compare the obtained results with similar data for the antifungal histidine-rich 12-mer peptide P113 (AKRHHGYKRKFH), a drug candidate known as PAC-113, one of the shortest and most active analogues of the natural antifungal histidine-rich peptide Hst 5. Methods: Peptides were synthesized by a solid phase method using a Fmoc-based strategy. To determine the antifungal activity of the peptides, we used the opportunistic fungus strain Candida albicans EMTK 34. The number of microorganisms (titer) in the suspension was determined by optical density at a wavelength of 595 nm. To determine the antifungal activity of the peptides, cell cultures were co-incubated with the studied peptides in 96-well plates. The cells were incubated with the drug for 24 h at 37°C. To assess the antifungal activity of the studied peptides, their minimum inhibitory concentrations (MIC50) were determined, i.e. such peptide concentration at which the growth of microorganisms was suppressed by 50%. To assess the toxicity of the peptides, their hemolytic activity was determined, which was tested against fresh human erythrocytes using a photometric method. To assess the selectivity of the action of peptides, the values of the minimum hemolytic concentration (MHC) of the peptides were determined and the values of their therapeutic index (TI) were calculated as the ratio of the minimum hemolytic concentration (MHC) to the MIC50 value. Results and Discussion: It was shown that the antifungal activity of the studied SAMPLTA increases with an increase in the number of histidine residues in their composition, reaching the maximum value for the histidine-containing peptide F2H16 (MIC50 = 1.0 µM). It has been shown that as the chain length of peptides increases, their hemolytic toxicity also increases. The TI values for these peptides were 233, 247, 79, and 60, respectively. It has been shown that, against C. albicans, histidine-containing SAMP-LTA derivatives with phenylalanine residues at the N-terminus of the peptide (F2H10) are less effective compared to similar peptides (H10F2) containing phenylalanine residues at the C-terminus. Among the studied peptides, the most active was the H10 peptide (MIC50 = 0.7 µM), which does not contain phenylalanine residues, which in its antifungal activity is not only more effective than all other histidine-containing peptides, including the F2H16 peptide with 16 histidine residues, but also 4– 5 times more effective than the antifungal peptide P113 (MIC50 = 3.4 µM), a short active fragment of natural Hst 5, well known from the literature. Among all the studied peptides, H10 and P113 have minimal (almost zero) values of hemolytic activity. However, due to its higher antifungal activity, the selectivity of the H10 peptide (TI > 1400) exceeds the selectivity of the P113 peptide (TI > 340) by more than 4 times. Conclusions: Thus, peptide H10, due to its high antifungal activity, low hemolytic toxicity and, accordingly, high therapeutic significance, can be used as a promising antifungal peptide drug. [ABSTRACT FROM AUTHOR]

In this study, we produced hydroxypropyl methylcellulose (HPMC) films containing silver nanoparticles (AgNPs) by a straightforward method for potential wound dressing applications. Polyvinylpyrrolidone (PVP) or polyvinyl alcohol (PVA) was added to these films to improve their mechanical properties. Various compositions of HPMC, PVP/PVA, and AgNPs were tested. The films containing AgNPs exhibited a yellow color, and the confirmation of silver nanoparticles was achieved through UV–Vis analysis. The antimicrobial capacity of HPMC films was assessed against strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. Pristine HPMC and HPMC films blended with PVA/PVP displayed no antimicrobial activity, emphasizing the essential role of silver nanoparticles. The films with the highest AgNP content effectively inhibited Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, surpassing the literature data. Some samples showed moderate inhibitory activity against Candida albicans. These films show potential as wound dressings, attributed to their antimicrobial properties and their convenient removal in the shower or by using a gentle water spray which may lead to reduced discomfort compared to traditional dressings. Further research is required to assess their clinical performance. [ABSTRACT FROM AUTHOR]

Fleagrass, a herb known for its pleasant aroma, is widely used as a mosquito repellent, antibacterial agent, and for treating colds, reducing swelling, and alleviating pain. The antifungal effects of the essential oils of fleagrass and carvacrol against Candida albicans were investigated by evaluating the growth and the mycelial and biofilm development of C. albicans. Transmission electron microscopy was used to evaluate the integrity of the cell membrane and cell wall of C. albicans. Fleagrass exhibited high fungicidal activity against C. albicans at concentrations of 0.5% v/v (via the Ras1/cAMP/PKA pathway). Furthermore, transmission electron microscopy revealed damage to the cell wall and membrane after treatment with the essential oil, which was further confirmed by the increased levels of β-1,3-glucan and chitin in the cell wall. This study showed that fleagrass exerts good fungicidal and hyphal growth inhibition activity against C. albicans by disrupting its cell wall, and thus, fleagrass may be a potential antifungal drug. [ABSTRACT FROM AUTHOR]

The present study explores the influence of Cobalt oxide nanoparticles(Co3O4 NPs) on the physicochemical characteristics of Poly(vinylalcohol)/ Chitosan (PVA/Cs) blend. Using a variety of techniques, the pure blend and the nanocomposites' composition, structure, optical, thermal, and mechanical properties, and antibacterial activity were characterized. The Co3O4 NPs were produced by precipitation method utilizing cobalt salt as the raw material. The crystalline nature of the nanoparticles and semi-crystalline behavior of the PVA/Cs are demonstrated by the XRD data. Adding nanoparticles to the pure blend reduced the intensity of the semi-crystalline. The rise in absorption intensity observed in UV-visible spectra upon the incorporation of Co3O4 NPs into the PVA/Cs blend indicates an improved dispersion of the nanoparticles within the blend. When Co3O4 NPs are added, the energy band-gap Egdir and Egind of PVA/Cs–Co3O4 samples greatly decrease. According to TGA data, the thermal stability of nanocomposites was significantly higher than that of the PVA/Cs blend, and it rose as the concentration of nanoparticles increased. When compared to neat PVA/Cs film, mechanical property investigation of PVA/Cs–Co3O4 nanocomposites films revealed enhanced features. The effectiveness of the PVA/Cs–Co3O4 nanocomposite films in inhibiting the growth of microorganisms was assessed by evaluating their antimicrobial activity (ANMAC) against a range of bacteria and fungi. The inclusion of Co3O4 NPs led to an increase in activity against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria as well as fungi Candida albicans and Aspergillus niger (C. albicans and A. niger). The addition of Co3O4 NPs to the PVA/Cs blend effectively improved the material's optical, thermal, mechanical, and antibacterial properties. This remarkable improvement stems from the Co3O4 NPs, which were introduced into the PVA/Cs blend in different amounts, leading to the development of novel nanocomposites. The outstanding properties of Co3O4/PVA/Cs nanocomposite films suggest their potential for applications in optoelectronics and food packaging. [ABSTRACT FROM AUTHOR]

The present work aims to develop and evaluate the wound healing potential of bakuchiol nanoemulsion loaded electrospun scaffolds. Since oxidative stress and microbial burden leads the burn wounds to become chronic and fatal to patients, a phytoconstituent, bakuchiol (BAK), was screened on the basis of antioxidant and antimicrobial potential which also defined its dose. Furthermore, BAK was incorporated into a nanoemulsion to enhance its therapeutic efficacy, reduce its dosage frequency, and maximize its stability. The present study is inclined towards the collaborative interaction of natural products and novel drug delivery systems to develop safe and therapeutically efficient systems for burn wound healing. The optimized nanoemulsion showed excellent antioxidant and antimicrobial potential against wound susceptible pathogens, i.e., Candida albicans and Methicillin-resistant Staphylococcus aureus which was further loaded into gelatin based hydrogel and nanofibrous scaffold system. The mesh structure of scaffolds was chosen as a suitable carrier system for wound healing process not only because it offers resemblance to skin's anatomy but is also capable of providing uniform distribution of wound biomarkers across the skin. The prepared nanofibers were assessed for their analgesic, anti-inflammatory, and wound healing potential which was observed to be significantly better than its gel formulation. [ABSTRACT FROM AUTHOR]

Commercial topical formulations containing itraconazole (poorly water soluble), for mycotic infections, have poor penetration to infection sites beneath the nails and skin thereby necessitating oral administration. To improve penetration, colloidal solutions of itraconazole (G1-G4) containing Poloxamer 188, tween 80, ethanol, and propylene glycol were prepared and incorporated into HFA-134-containing sprays. Formulations were characterized using particle size, drug content, and Fourier-transform infrared spectroscopy (FTIR). In vitro permeation studies were performed using Franz diffusion cells for 8 h. Antimycotic activity on Candida albicans and Trichophyton rubrum was performed using broth micro-dilution and flow cytometry, while cytotoxicity was tested on HaCaT cell lines. Particle size ranged from 39.35–116.80 nm. FTIR and drug content revealed that G1 was the most stable formulation (optimized formulation). In vitro release over 2 h was 45% for G1 and 34% for the cream. There was a twofold increase in skin permeation, fivefold intradermal retention, and a sevenfold increase in nail penetration of G1 over the cream. Minimum fungicidal concentrations (MFC) against C. albicans were 0.156 and 0.313 µg/mL for G1 and cream, respectively. The formulations showed optimum killing kinetics after 48 h. MFC values against T. rubrum were 0.312 and 0.625 µg/mL for the G1 and cream, respectively. Transmission electron microscopy revealed organelle destruction and cell leakage for G1 in both organisms and penetration of keratin layers to destroy T. rubrum. Cytotoxicity evaluation of G1 showed relative safety for skin cells. The G1 formulation showed superior skin permeation, nail penetration, and fungicidal activity compared with the cream formulation. [ABSTRACT FROM AUTHOR]

Candida albicans is one of the most dangerous pathogenic fungi in the world, according to the classification of the World Health Organization, due to the continued development of its resistance to currently available anticandidal agents. To overcome this problem, the current work provided a simple, one-step, cost-effective, and safe technique for the biosynthesis of new functionalized anticandidal selenium nanoparticles (Se NPs) against C. albicans ATCC10231 using the cell-free supernatant of Limosilactobacillus fermentum (OR553490) strain. The bacterial strain was isolated from yogurt samples available in supermarkets, in Damietta, Egypt. The mixing ratio of 1:9 v/v% between cell-free bacterial metabolites and sodium selenite (5 mM) for 72 h at 37 °C were the optimum conditions for Se NPs biosynthesis. Ultraviolet–visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD), Zeta analyses, and elemental analysis system (EDS) were used to evaluate the optimized Se NPs. The Se NPs absorption peak appeared at 254 nm. Physicochemical analysis of Se NPs revealed the crystalline-shaped and well-dispersed formation of NPs with an average particle size of 17–30 nm. Se NPs have − 11.8 mV, as seen by the zeta potential graph. FT-IR spectrum displayed bands of symmetric and asymmetric amines at 3279.36 cm−1 and 2928.38 cm−1, aromatic and aliphatic (C–N) at 1393.32 cm−1 and 1237.11.37 cm−1 confirming the presence of proteins as stabilizing and capping agents. Se NPs acted as a superior inhibitor of C. albicans with an inhibition zone of 26 ± 0.03 mm and MIC value of 15 µg/mL compared to one of the traditional anticandidal agent, miconazole, which revealed 18 ± 0.14 mm and 75 µg/mL. The cytotoxicity test shows that Se NPs have a low toxic effect on the normal keratinocyte (IC50 ≈ 41.5 μg/mL). The results indicate that this green synthesis of Se NPs may have a promising potential to provide a new strategy for drug therapy. [ABSTRACT FROM AUTHOR]

Candida auris is an emerging pathogenic yeast that has been categorized as a global public health threat and a critical priority among fungal pathogens. Despite this, the immune response against C. auris infection is still not well understood. Hosts fight Candida infections through the immune system that recognizes pathogen-associated molecular patterns such as β-glucan, mannan, and chitin on the fungal cell wall. In this study, levels of β-glucan and mannan exposures in C. auris grown under different physiologically relevant stimuli were quantified by flow cytometry-based analysis. Lactate, hypoxia, and sublethal concentration of fluconazole trigger a decrease in surface β-glucan while low pH triggers an increase in β-glucan. There is no inverse pattern between exposure levels of β-glucan and mannan in the cell wall architecture among the three clades. To determine the effect of cell wall remodeling on the immune response, a phagocytosis assay was performed, followed by quantification of released cytokines by ELISA. Lactate-induced decrease in β-glucan leads to reduced uptake of C. auris by PMA-differentiated THP-1 and RAW 264.7 macrophages. Furthermore, reduced production of CCL3/MIP-1⍺ but not TNF-⍺ and IL-10 were observed. An in vivo infection analysis using silkworms reveals that a reduction in β-glucan triggers an increase in the virulence of C. auris. This study demonstrates that β-glucan alteration occurs in C. auris and serves as an escape mechanism from immune cells leading to increased virulence. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) synthesized via a green method offer numerous advantages compared to conventional chemical synthesis routes, primarily due to their lower cost, non-toxic nature, and enhanced antimicrobial properties. This study introduces a green method for synthesizing AgNPs with promising antimicrobial properties, using Kappaphycus alvarezii (K. alvarezii), a red seaweed, as the reducing and stabilizing agent. The hydrothermal method was employed, and optimal synthesis conditions were identified at 90 °C for 2 h. The resulting AgNPs were comprehensively characterized using an array of spectroscopic and microscopic techniques including UV–Visible (UV–Vis) spectroscopy, fourier-transform infrared spectroscopy, X-ray diffraction spectroscopy, energy-dispersive X-ray spectroscopy, field emission scanning electron microscopy, transmission electron microscope, and atomic force microscopy. The findings indicated that the functional groups inherent to the seaweed extract played a crucial role in both reducing and stabilizing the AgNPs. The synthesized AgNPs are confirmed based on the presence of the characteristic surface plasmon resonance band within the 380–460 nm range in the UV–Vis spectra. The AgNPs are predominantly composed of silver (82.38 wt%) and exhibit a face-centered cubic lattice based on the distinct diffraction peaks observed at 2θ values of 38.06°, 44.23°, 64.34°, and 77.27° align with the (1 1 1), (2 0 0), (2 2 0), and (3 1 1) reflection planes. Microscopic analysis revealed a cubical shape of the nanoparticles with rough surfaces consisting of spherical nanoparticles measuring 1–8 nm in diameter. The AgNPs displayed potent antimicrobial activity against a range of pathogens including Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Staphylococus aureus (S. aureus), Bacillus subtilis subsp. spizizenii (B. subtilis), and Candida albicans (C. albicans) with minimum inhibitory concentrations and minimum bactericidal/fungicidal concentrations as low as 0.13 mg/mL. These findings highlight the potential of K. alvarezii as reducing agent for the production of AgNPs, which hold great promise as antimicrobial agents in various food and biomedical applications. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate the efficacy of denture cleaners on the adhesion of Candida albicans and their effects on the surface, optical, and mechanical properties of resins for conventional, milled, and 3D-printed denture bases. Materials and methods: A total of 240 resin samples were made, 120 for testing Candida albicans adhesion, optical stabilities (ΔE00), roughness (Ra), hydrophilicity (°), surface free energy (Owens-Wendt) and 120 samples for testing Candida albicans adhesion, surface microhardness (Knoop), flexural strength and modulus of elasticity in a three-point test, in which they were divided into 3 groups of denture resin (n = 40) and subdivided into 5 cleaners of dentures (n = 8). Data were evaluated by two-way ANOVA and Tukey’s test for multiple comparisons (α = 0.05). Results: Denture cleaners with an alkaline solution and dilute acid composition were those that showed the greatest effectiveness in reducing Candida albicans (P < 0.001), however 1% NaOCl significantly affected the properties of the resins (P < 0.05). Denture 3D-printed showed that the surface microhardness was significantly lower for all cleansers (P < 0.05). Conclusions: Listerine demonstrated superior efficacy in reducing Candida albicans with minimal effect on denture properties, whereas 1% NaOCl had a significant negative impact on the properties. The mechanical properties were significantly lower in 3D-printed resin than in other resins for all denture cleansers. Clinical relevance: Denture base materials are being sold to adapt to the CAD/CAM system, increasing the number of users of dentures manufactured with this system. Despite this, there is little investigation into denture cleaners regarding the adhesion capacity of microorganisms and the optical, surface and mechanical properties of dentures, thus requiring further investigation. [ABSTRACT FROM AUTHOR]

This study aimed to assess the in vitro probiotic and antioxidant potential of lactic acid bacteria (LAB) isolated from different white cheeses, also known as "Beyaz Peynir" in Turkey. A total of 58 bacterial strains were isolated from 11 different white cheeses obtained from small-scale dairies. According to some preselection criteria (having the distinctive features of LAB, exhibiting non-haemolytic property, and resisting the simulated gastrointestinal conditions such as low pH, pepsin, pancreatin and bile salt tolerance), four (ED13, ED20, ED25 and ED36) out of 58 isolates were selected for the subsequent experiments. Among the four isolates, ED25 exhibited the maximum lactase production and cholesterol removal potential, the highest biological activity (antimicrobial and antioxidant activity) and the lowest antibiotic resistance. In addition, the second highest B12-producing capacity were measured for ED25. The isolate ED25 was found to possess antimicrobial effectiveness against all tested microorganisms (S. aureus, E. coli, S. Typhimurium, L. monocytogenes and C. albicans) according to the agar well diffusion method. In vitro antioxidant activity assay demonstrated that the culture supernatant of the ED25 had the ability to scavenge DPPH (49%), ABTS (37%), OH• (51%) and O2•– (38%) radicals. According to the sequences analysis of the 16 S rRNA gene, the isolate ED25 was identified as Lacticaseibacillus paracasei (GenBank accesion number: OP036674.1). Due to strong biological activities, L. paracasei ED25 may be used as a probiotic agent against gastrointestinal disorders, infections and oxidative stress-mediated diseases. [ABSTRACT FROM AUTHOR]

Candida albicans is known for its pathogenicity, although it lives within the human body as a commensal member. The commensal nature of C. albicans is well controlled and regulated by the host's immune system as they live in the harmonized microenvironment. However, the development of certain unusual microhabitat conditions (change in pH, co-inhabiting microorganisms' population ratio, debilitated host-immune system) pokes this commensal fungus to transform into a pathogen in such a way that it starts to propagate very rapidly and tries to breach the epithelial barrier to enter the host's systemic circulations. In addition, Candida is infamous as a major nosocomial (hospital-acquired infection) agent because it enters the human body through venous catheters or medical prostheses. The hysterical mode of C. albicans growth builds its microcolony or biofilm, which is pathogenic for the host. Biofilms propose additional resistance mechanisms from host immunity or extracellular chemicals to aid their survival. Differential gene expressions and regulations within the biofilms cause altered morphology and metabolism. The genes associated with adhesiveness, hyphal/pseudo-hyphal growth, persister cell transformation, and biofilm formation by C. albicans are controlled by myriads of cell-signaling regulators. These genes' transcription is controlled by different molecular determinants like transcription factors and regulators. Therefore, this review has focused discussion on host-immune-sensing molecular determinants of Candida during biofilm formation, regulatory descriptors (secondary messengers, regulatory RNAs, transcription factors) of Candida involved in biofilm formation that could enable small-molecule drug discovery against these molecular determinants, and lead to disrupt the well-structured Candida biofilms effectively. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant portion of women worldwide. Licochalcone A (LA), a natural compound with diverse biological activities, holds promise as a protective agent against Candida albicans (C. albicans) infection. This study aims to investigate the potential of LA to safeguard vaginal epithelial cells (VECs) from C. albicans infection and elucidate the underlying molecular mechanisms. To simulate VVC in vitro, VK2-E6E7 cells were infected with C. albicans. Candida albicans biofilm formation, C. albicans adhesion to VK2-E6E7 cells, and C. albicans-induced cell damage and inflammatory responses were assessed by XTT reduction assay, fluorescence assay, LDH assay, and ELISA. CCK-8 assay was performed to evaluate the cytotoxic effects of LA on VK2-E6E7 cells. Western blotting assay was performed to detect protein expression. LA dose-dependently hindered C. albicans biofilm formation and adhesion to VK2-E6E7 cells. Furthermore, LA mitigated cell damage, inhibited the Bax/Bcl-2 ratio, and attenuated the secretion of pro-inflammatory cytokines in C. albicans-induced VK2-E6E7 cells. The investigation into LA's impact on the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway revealed that LA downregulated TLR4 expression and inhibited NF-κB activation in C. albicans-infected VK2-E6E7 cells. Furthermore, TLR4 overexpression partially abated LA-mediated protection, further highlighting the role of the TLR4/NF-κB pathway. LA holds the potential to safeguard VECs against C. albicans infection, potentially offering therapeutic avenues for VVC management. [ABSTRACT FROM AUTHOR]

Vaginitis, a prevalent gynecological condition in women, is mainly caused by an imbalance in the vaginal micro-ecology. The two most common types of vaginitis are vaginal bacteriosis and vulvovaginal candidiasis, triggered by the virulent Gardnerella vaginalis and Candida albicans, respectively. In this study, a strain capable of inhibiting G. vaginalis and C. albicans was screened from vaginal secretions and identified as Lactobacillus gasseri based on 16S rRNA sequences. The strain, named L. gasseri VHProbi E09, could inhibit the growth of G. vaginalis and C. albicans under co-culture conditions by 99.07% ± 0.26% and 99.95% ± 0.01%, respectively. In addition, it could significantly inhibit the adhesion of these pathogens to vaginal epithelial cells. The strain further showed the ability to inhibit the enteropathogenic bacteria Escherichia coli and Salmonella enteritidis, to tolerate artificial gastric and intestinal fluids and to adhere to intestinal Caco-2 cells. These results suggest that L. gasseri VHProbi E09 holds promise for clinical trials and animal studies whether administered orally or directly into the vagina. Whole-genome analysis also revealed a genome consisting of 1752 genes for L. gasseri VHProbi E09, with subsequent analyses identifying seven genes related to adhesion and three genes related to bacteriocins. These adhesion- and bacteriocin-related genes provide a theoretical basis for understanding the mechanism of bacterial inhibition of the strain. The research conducted in this study suggests that L. gasseri VHProbi E09 may be considered as a potential probiotic, and further research can delve deeper into its efficacy as an agent which can restore a healthy vaginal ecosystem. [ABSTRACT FROM AUTHOR]

The antibacterial characteristics of graphene oxide (GO-SB) nano-sheets generated by charring sugarcane bagasse (SB) are described in this study. The antibacterial capability of GO-SB was improved when it was grafted with ethyl cellulose (EC) and polyvinyl alcohol (PVA) to form GO-SB/EC/PVA hydrogels. Characterization of GO-SB nanosheets and GO-SB/EC/PVA hydrogels was accomplished by using FTIR, SEM, XRD, and thermal studies. The antimicrobial activity was carried out against Gram positive bacteria [Micrococcus leutus & Staphylococcus aureus], Gram negative bacteria [Escherichia coli, Pseudomonas aeruginosa] and pathogenic fungal yeast [Candida albicans] applying the disc diffusion method. The disc diffusion method results showed that the improved GO-SB/EC/PVA exhibited a reasonable level of antimicrobial capability against Micrococcus leutus, demonstrating that the antimicrobial improvement of GO-SB was more effective in the GO-SB/EC/PVA hydrogels by increasing the inhibition zone of Gram-positive bacteria, Micrococcus leutus from (13.0 to 16.0 mm). [ABSTRACT FROM AUTHOR]

Candida albicans is among the most prevalent invasive fungal pathogens for immunocompromised individuals and novel therapeutic approaches that involve immune response modulation are imperative. Absent in melanoma 2 (AIM2), a pattern recognition receptor for DNA sensing, is well recognized for its involvement in inflammasome formation and its crucial role in safeguarding the host against various pathogenic infections. However, the role of AIM2 in host defense against C. albicans infection remains uncertain. This study reveals that the gene expression of AIM2 is induced in human and mouse innate immune cells or tissues after C. albicans infection. Furthermore, compared to their wild-type (WT) counterparts, Aim2−/− mice surprisingly exhibit resistance to C. albicans infection, along with reduced inflammation in the kidneys post-infection. The resistance of Aim2−/− mice to C. albicans infection is not reliant on inflammasome or type I interferon production. Instead, Aim2−/− mice display lower levels of apoptosis in kidney tissues following infection than WT mice. The deficiency of AIM2 in macrophages, but not in dendritic cells, results in a phenocopy of the resistance observed in Aim2−/− mice against C. albican infection. The treatment of Clodronate Liposome, a reagent that depletes macrophages, also shows the critical role of macrophages in host defense against C. albican infection in Aim2−/− mice. Furthermore, the reduction in apoptosis is observed in Aim2−/− mouse macrophages following infection or treatment of DNA from C. albicans in comparison with controls. Additionally, higher levels of AKT activation are observed in Aim2−/− mice, and treatment with an AKT inhibitor reverses the host resistance to C. albicans infection. The findings collectively demonstrate that AIM2 exerts a negative regulatory effect on AKT activation and enhances macrophage apoptosis, ultimately compromising host defense against C. albicans infection. This suggests that AIM2 and AKT may represent promising therapeutic targets for the management of fungal infections. [ABSTRACT FROM AUTHOR]

Effective disinfection methods are crucial in the cold chain transportation process of food due to the specificity of temperature and the diversity of contaminated flora. The objective of this study was to investigate the sanitizing effect of different disinfectants on various fungi at – 20 °C to achieve accurate disinfection of diverse bacterial populations. Peracetic acid, hydrogen peroxide, and potassium bisulfate were selected as low-temperature disinfectants and were combined with antifreeze. The sanitizing effect of these cryogenic disinfectants on pathogens such as Bacillus subtilis black variant spores (ATCC9372), Staphylococcus aureus (ATCC 6538), Candida albicans (ATCC 10231), Escherichia coli (8099), and poliovirus (PV-1) was sequentially verified by bactericidal and virus inactivation experiments. After a specified time of disinfection, a neutralizing agent was used to halt the sanitizing process. The study demonstrates that different disinfectants exhibit selective effects during the low-temperature disinfection process. Peracetic acid, hydrogen peroxide, and potassium monopersulfate are suitable for the low-temperature environmental disinfection of bacterial propagules, viruses, and fungal contaminants. However, for microorganisms with strong resistance to spores, a low-temperature disinfectant based on peracetic acid should be chosen for effective disinfection treatment. Our results provide a valuable reference for selecting appropriate disinfectants to sanitize various potential pathogens in the future. [ABSTRACT FROM AUTHOR]

The prevalence of Candida albicans infection has increased during the past few years, which contributes to the need for new, effective treatments due to the increasing concerns regarding antifungal drug toxicity and multidrug resistance. Butyl isothiocyanate (butylITC) is a glucosinolate derivative, and has shown a significant antifungal effect contrary to Candida albicans. Additionally, how butylITC affects the virulence traits of C. albicans and molecular mode of actions are not well known. Present study shows that at 17.36 mM concentration butylITC inhibit planktonic growth. butylITC initially slowed the hyphal transition at 0.542 mM concentration. butylITC hampered biofilm development, and inhibits biofilm formation at 17.36 mM concentration which was analysed using metabolic assay (XTT assay) and Scanning Electron Microscopy (SEM). In addition, it was noted that butylITC inhibits ergosterol biosynthesis. The permeability of cell membranes was enhanced by butylITC treatment. Moreover, butylITC arrests cells at S-phase and induces intracellular Reactive Oxygen Species (ROS) accumulation in C. albicans. The results suggest that butylITC may have a dual mode of action, inhibit virulence factors and modulate cellular processes like inhibit ergosterol biosynthesis, cell cycle arrest, induces ROS production which leads to cell death in C. albicans. [ABSTRACT FROM AUTHOR]

Vaginal lactobacilli protect against bacterial vaginosis and vaginal candidiasis. They may have probiotic properties and help maintain the balance and health of the vaginal ecosystem while the loss of these bacteria predisposes females to urinary and genital infections. The aim of this study was to investigate the probiotic potential of vaginal Lactobacillus among healthy females in northern Iran. The Lactobacillus strains were isolated from vaginal samples and were identified by sequencing of the 16S rRNA fragment. Functional properties such as tolerance to low pH, H2O2 production, adherence ability to Hela cells and antagonistic activity against Candida albicans was examined. A total of 38 vaginal lactobacilli strains from five species, including Lactobacillus crispatus (n = 13), Lactobacillus gasseri (n = 10), Lactobacillus acidophilus (n = 6), Lactobacillus jensenii (n = 5) and Lactobacillus johnsonii (n = 4), were identified. All of the species showed significant tolerance to low pH over 24 h (p < 0.001). The best adherence ability to Hela cells was seen in Lactobacillus gasseri strains. Nearly 17 of the strains had higher anti-candida activity compared to the other strains. According to the findings, four lactobacilli strains isolated in the vaginal samples of healthy Iranian women had the best probiotic potential. [ABSTRACT FROM AUTHOR]

The human oral cavity is normally colonized by microorganisms including bacteria, fungi, archaea, viruses and protozoa. The aim of this study was to determine the frequency of Candida spp., in de oral cavity in a group of medical students from the north of Mexico. Oral sample were obtained from 240 healthy students. The specimens were analyzed by traditional microbiology cultures and DNA sequencing. Candida spp., grew in Sabouraud dextrose agar from 57 samples and subsequently were isolated and phenotyped. The definitive identification to the species level was done by sequence analysis. The yeasts were identified as follow: 28 Clavispora lusitaniae, 20 Candida albicans, 5 Pichia kudriavzevii and 4 Candida parapsilosis. Our findings revealed that 23.75% of the healthy population has a potential pathogen in their mouth. Surprisingly, C. albicans is not the predominant yeast; instead other non-Candida species are the colonizers of the oral cavity as normal microbiota. C. lusitaniae is considered an emerging opportunistic pathogen in immunosuppressive patients. This paper pretends to highlight the presence of this yeast in the oral cavity in immunocompetent young adults. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess risk factors of candida-related Vascular Graft Infections (VGIs). Methods: We did a case–control study (1:4) matched by age and year of infection, nested in a cohort of patient with a history of VGIs. Cases were defined by a positive culture for Candida spp. in biological samples and controls were defined by a positive culture for bacterial strains only in biological samples. Risk factors for Candida-related VGIs were investigated using multivariate logistic regression. Mortality were compared using survival analysis. Results: 16 Candida-related VGIs were matched to 64 bacterial-related VGIs. The two groups were comparable regarding medical history and clinical presentation. Candida-related VGIs were associated with bacterial strains in 88% (14/16). Gas/fluid-containing collection on abdominal CT scan and the presence of an aortic endoprosthesis were risk factors for Candidaspp.-related VGIs [RRa 10.43 [1.81–60.21] p = 0.009 RRa and 6.46 [1.17–35.73] p = 0.03, respectively]. Candida-related VGIs were associated with a higher mortality when compared to bacterial-related VGIs (p = 0.002). Conclusions: Candida-related VGIs are severe. Early markers of Candidaspp. infection are needed to improve their outcome. The suspicion of aortic endoprosthesis infection may necessitate probabilistic treatment with antifungal agents. [ABSTRACT FROM AUTHOR]

Fluconazole (FLZ) has been widely used in the treatment of infection caused by Candida albicans, including the treatment of vulvovaginal candidiasis (VVC). However, when delivered orally, FLZ faces numerous limitations due to its poor solubility and undergoes the symptoms of first-pass metabolism. In this study, we developed the combinatorial approach of nanocrystals (NCs) and dissolving microneedles (DMNs) for effective local vaginal delivery of FLZ. The formulation containing 1.0% w/v PVA as stabilizer with 12 h of milling time process was found to be an optimal combination to fabricate FLZ as NCs (FLZ-NCs) with optimum size particle and PDI value (less than 0.25). Furthermore, the in vitro release study also showed a superior percentage of FLZ release up to 89.51 ± 7.52%. In combination with the DMNs, the FLZ recovery was 96.45 ± 2.38% with the insertion percentage in average of 76.14 ± 2.28% and height decreased percentage was only 7.53 ± 0.56%. Moreover, the ex vivo investigation and anti-candidiasis activity of DMNs-FLZ-NCs in vaginal model showed better results compared to other conventional preparations, such as film patch and hydrogel containing FLZ. [ABSTRACT FROM AUTHOR]

The recent emergence of drug-resistant microorganisms and the prevalence of cancer diseases are both presenting substantial global public health concerns. Silver nanoparticles (AgNPs) have attracted significant attention and are increasingly employed in diverse biomedical applications as agents with antimicrobial and anticancer properties. The study herein focused on the biogenic synthesis of AgNPs employing the cell-free filtrate of the soil-derived bacterium Streptomyces pratensis as a reducing agent. AgNPs were characterized using UV–Vis, FTIR, FE-SEM, and TEM. The study assessed both the antibacterial and anticandidal modes of action, along with the potential anticancer properties of the biosynthesized AgNPs. The spherical, 17–44-nm biosynthesized AgNPs demonstrated strong antimicrobial and antibiofilm activities against pandrug-resistant (PDR) Gram-negative Klebsiella pneumoniae and pathogenic yeast Candida albicans, both of which were isolated from immunosuppressed patients. Dose-dependent interactions between the AgNPs and their anticancer activity were observed. The IC50 values of the AgNPs against the hepatocellular (HepG2) and colon carcinoma (HCT-116) cancer cell lines were approximately 16.5 µg/mL and 11.5 µg/mL, respectively. Furthermore, the antimicrobial mechanism of action of AgNPs revealed distinct leakage of sugar, DNA, and proteins from the cell membrane of both K. pneumoniae and C. albicans, as well as increased ROS generation. Moreover, the TEM micrographs depicted the distortion and damage experienced by the microbial cells after exposure to AgNPs. The findings of the current study suggest that biosynthesized AgNPs have the potential to serve as alternative therapeutic agents for combating drug-resistant K. pneumoniae, the yeast C. albicans, in addition to HepG2 and HCT-116 cells. [ABSTRACT FROM AUTHOR]

The continuous search for more effective options against well-known pathogens such as Candida albicans remains the rationale for the search for novel lead compounds from various sources. This study aims to investigate the chemical structure, chemical properties, of 5-(2-((5-(((1S,3R) -3-(5-acetamido-1,3,4-thiadiazolidin-2-yl) cyclopentyl) methyl)-1,3,4-thiadiazolidin-2-yl)amino)-2-oxoethyl)-2-methyl-2,3-dihydro-1H-pyrazol-3-ide designated ATCTP using DFT method ωB97XD/-311 + + g(2d, 2p) and the biological potential of compound ATCTP against Candida albicans using molecular docking and ADMET studies. Geometry optimization was carried out in DMSO, ethanol. gas and water revealing minute discrepancies in bond length and wider differences in bond angles. Frontier molecular orbital investigations reveal HOMO–LUMO energy gap magnitude in decreasing order of ATCTP_Gas > ATCTP_Water > ATCTP_ethanol > ATCTP_DMSO inferring that water influences chemical stability of the compound the most compared to ethanol and DMSO. Density of state investigations have revealed electron density contributions at corresponding energy peaks. In silico pharmacokinetic predicts ATCTP not to be cytotoxic, hepatotoxic, immunotoxic or mutagenic but probable mutagen. Molecular docking investigation of ATCTP against aspartic proteinase of Candida albicans (ID: 2QZX) in comparison with standard drug Fluconazole. Compound ATCTP had higher binding affinity (− 8.1 kcal/mol) compared to that of the standard drug fluconazole (− 5.6 kcal/mol) which records 4 conventional hydrogen interactions compared to 2 formed in the interaction of ATCTP + 2QZX. ATCTP also reports binding affinity of − 7.2 kcal/mol which reportedly surpassed that of 2QZX interaction with fluconazole (− 5.7 kcal/mol). ATCTP binds with lanosterol14-α-demethylase (5v5z) with binding affinity of − 9.7 kcal/mol binding to active site amino acid residues of the protein compared to fluconazole + 5v5z (− 8.0 kcal/mol). ATCTP is therefore recommended to be a lead compound for the possible design of a new and more effective anti-candida therapeutic compound. [ABSTRACT FROM AUTHOR]

Background: Characterization of yeast virulence genes is an important tool for identifying the molecular pathways involved in switching yeast virulence. Biofilm formation (BF) and secreted aspartic proteinase (SAP) activity are essential virulence factors that contribute to yeast pathogenicity. Results: Four Candida albicans and two Saccharomyces cerevisiae strains were tested for BF and SAP activity under optimum conditions, and the expression levels of several genes controlling BF were quantified under the optimal conditions. Biofilm formation was assessed by the microplate method at different pH values, incubation times and culture media. Similarly, SAP activity was assessed at different pH values and incubation periods. The expression levels of nine genes were determined via qRT-PCR technique. All tests were carried out in triplicate, and the values presented as the means ± standard deviations and were analysed with the SPSS programme. Only C. albicans (1), C. albicans (2) and S. cerevisiae 43 formed biofilms. The optimal BF was obtained after culture in sabouraud dextrose broth with 8% glucose at pH 7.5, 4 and 6, respectively, for 48h. Candida albicans biofilm production was more significant than that of S. cerevisiae 43. Moreover, the SAP activity was estimated under the optimum conditions. All yeasts showed optimal SAP activity at pH 4, but astonishingly the SAP activity of S. cerevisiae 44 was higher than that of C. albicans. The expression levels of EFG1 and ZAP1 (transcription factors); ALS3, HWP1and YWP1 (adhesion genes); SAP1 and SAP4 (aspartic proteinase) in C. albicans (1); and FLO11 (adhesion gene) and YPS3 (aspartic proteinase) in S. cerevisiae 43 were quantified during biofilm development at different time intervals. The expression levels of EFG1, ALS3, YWP1, SAP1, SAP4, FLO11 and YPS3 were upregulated at 8 h, while that of ZAP1 was upregulated at 48 h. Only HWP1 was downregulated. Conclusions: The findings of the present study may provide information for overcoming yeast BF and pathogenicity by regulating specific genes at specific times. Additionally, this study revealed the virulence of the commensal S. cerevisiae, which may take the pathogenicity direction as C. albicans. [ABSTRACT FROM AUTHOR]

Candida is the most prevalent fungal bloodstream infection (BSI) with a high mortality rate among hospitalized patients. Another concern facing physicians is rising global incidence of drug-resistant Candida. This study aimed to characterize the prevalence, antifungal susceptibility, biofilm formation, and virulence genes (HWP1, ALS1, SAP2) of different Candida spp. isolated from patients with candidemia. 52 isolates of Candida spp. were identified from blood cultures by chromogenic Candida agar and confirmed by the VITEK 2 system. Isolates were tested for antifungal susceptibility by disk diffusion and VITEK 2 system. Biofilm formation and investigated genes were detected by the Congo red method and conventional PCR, respectively. Candida spp. caused 2.3% of detected BSIs, of which 32.7% were caused by Candida albicans (C. albicans) and 67.3% by non-albicans Candida (NAC), with the predominance of C. tropicalis (25%), followed by C. parapsilosis (17.3%), and C. krusei (13.5%). The susceptibility rates to fluconazole, voriconazole, caspofungin, micafungin, amphotericin B, and flucytosine were 64.7%, 76.5%, 100.0%, 100%, 100.0%, and 100.0% in C. albicans, while 53.6%, 71.4%, 91.4%, 91.4%, 94.3%, and 94.3% in NAC, respectively. Biofilm production, HWP1, ALS1, and SAP2 were detected in 70.6%, 82.4%, 76.5%, and 52.9% of C. albicans and 74.3%, 85.7%, 80.0%, and 48.6% of NAC, respectively. There is remarkable shift to NAC BSIs and high azole resistance. Antifungal stewardship and analysis of risk factors associated with this shift are needed. [ABSTRACT FROM AUTHOR]

Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B (1) and C (2) together with known saroclazin A (3) (4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien (4). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B (1) as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in fungal pathogens (both human and plant) is increasing alarmingly, leading to massive economic crises. The existing anti-fungal agents are becoming ineffective, and the situation worsens on a logarithmic scale. Novel antifungals from unique natural sources are highly sought to cope sustainably with the situation. Metabolites from endophytic microbes are the best-fitted alternatives in this case. Endophytes are the untapped sources of 'plants' internal microbial population' and are promising sources of effective bio-therapeutic agents. Fungal endophytes were isolated from Tropaeolum majus and checked for antifungal activity against selected plant and human pathogens. Bioactive metabolites were identified through chromatographic techniques. The mode of action of those metabolites was evaluated through various spectroscopic techniques. The production of antifungal metabolite was optimized also. In particular VOCs (volatile organic compounds) of TML9 were tested in vitro for their anti-phytopathogenic activity. Ethyl acetate (EA) extract of cell-free culture components of Colletotrichum aenigma TML3 exhibited broad-spectrum antifungal activity against four species of Candida and the major constituents reported were 6-pentyl-2H-pyran-2-one, 2-Nonanone, 1 propanol 2-amino. The volatile metabolites, trans-ocimene, geraniol, and 4-terpinyl acetate, produced from Curvularia lunata TML9, inhibited the growth of some selected phyto pathogens. EA extract hampered the biofilm formation, minimised the haemolytic effect, and blocked the transformation of Candida albicans (MTCC 4748) from yeast to hyphal form with a Minimum Fungicidal Concentration (MFC) of 200–600 µg mL−1. Central carbohydrate metabolism, ergosterol synthesis, and membrane permeability were adversely affected and caused the lethal leakage of necessary macromolecules of C. albicans. Volatile metabolites inhibited the growth of phytopathogens i.e., Rhizoctonia solani, Alternaria alternata, Botrytis cinerea, Cercospora beticola, Penicillium digitatum, Aspergillus fumigatus, Ceratocystis ulmi, Pythium ultimum up to 89% with an IC50 value of 21.3–69.6 µL 50 mL−1 and caused leakage of soluble proteins and other intracellular molecules. Citrusy sweet odor volatiles of TML9 cultured in wheat-husk minimised the infections of Penicillium digitatum (green mold), in VOC-exposed sweet oranges (Citrus sinensis). Volatile and non-volatile antifungal metabolites of these two T. majus endophytes hold agricultural and pharmaceutical interests. Metabolites of TML3 have strong anti-Candida activity and require further assessment for therapeutic applications. Also, volatile metabolites of TML9 can be further studied as a source of antifungals. The present investigational outcomes bio-prospects the efficacy of fungal endophytes of Garden Nasturtium. [ABSTRACT FROM AUTHOR]

The transition between yeast and hyphae is crucial for regulating the commensalism and pathogenicity in Candida albicans. The mechanisms that affect the invasion of hyphae in solid media, whose deficiency is more related to the pathogenicity of C. albicans, have not been elucidated. Here, we found that the disruption of VAM6 or VPS41 which are components of the homotypic vacuolar fusion and protein sorting (HOPS) complex, or the Rab GTPase YPT72, all responsible for vacuole fusion, led to defects in hyphal growth in both liquid and solid media, but more pronounced on solid agar. The phenotypes of vac8Δ/Δ and GTR1OE-vam6Δ/Δ mutants indicated that these deficiencies are mainly caused by the reduced mechanical forces that drive agar and organs penetration, and confirmed that large vacuoles are required for hyphal mechanical penetration. In summary, our study revealed that large vacuoles generated by vacuolar fusion support hyphal penetration and provided a perspective to refocus attention on the role of solid agar in evaluating C. albicans invasion. The transition between yeast and hyphae is crucial for the pathogenicity of Candida albicans. Here, Liu et al. show that vacuole fusion is active during hyphal extension and that large vacuoles increase the mechanical forces of hyphae penetrating into organs. [ABSTRACT FROM AUTHOR]

Patients with decreased levels of CD18 (β2 integrins) suffer from life-threatening bacterial and fungal infections. CD11b, the α subunit of integrin CR3 (CD11b/CD18, αMβ2), is essential for mice to fight against systemic Candida albicans infections. Live elongating C. albicans activates CR3 in immune cells. However, the hyphal ligands that activate CR3 are not well defined. Here, we discovered that the C. albicans Als family proteins are recognized by the I domain of CD11b in macrophages. This recognition synergizes with the β-glucan-bound lectin-like domain to activate CR3, thereby promoting Syk signaling and inflammasome activation. Dectin-2 activation serves as the "outside-in signaling" for CR3 activation at the entry site of incompletely sealed phagosomes, where a thick cuff of F-actin forms to strengthen the local interaction. In vitro, CD18 partially contributes to IL-1β release from dendritic cells induced by purified hyphal Als3. In vivo, Als3 is vital for C. albicans clearance in mouse kidneys. These findings uncover a novel family of ligands for the CR3 I domain that promotes fungal clearance. Integrin CR3 (CD11b/CD18) is a receptor responsible for recognizing fungal β-glucan. Here, Zhou et al show that the Candida albicans Als family proteins are ligands for the CD11b I domain; an interaction which synergizes with β-glucan to activate CR3. [ABSTRACT FROM AUTHOR]

The antibacterial, antifungal, and analgesic activities of compounds of several sodium salts of 1-aryl-4,4,4-trifluorobutane-1,3-diones have been studied. These compounds have been found to exhibit a pronounced effect on Candida albicans (minimum inhibitory concentration, 7.8–62.5 μg/mL). The studied compounds showed significant antibacterial activity against cultures of Staphylococcus aureus (minimum inhibitory concentration, 2.0–31.2 μg/mL) and Escherichia coli (minimum inhibitory concentration 7.8–250.0 μg/mL). In addition, all compounds have pronounced analgesic activity, which exceeds that of the reference drug (metamizole sodium). [ABSTRACT FROM AUTHOR]

New derivatives of 3-R-5-chloromethyl-1-thiocarbamoylpyrazole have been synthesized by the intramolecular heterocyclization of thiosemicarbazones of unsaturated ketones, obtained by the interaction of 3,4-dichlorobut-2-ene-1-ones with thiosemicarbazide, in a dioxane with a twofold excess of pyridine. The biological activity of a series of the synthesized substances in vitro has been studied and it has been revealed that the synthesized functional derivatives of pyrazoles show more expressed antimicrobial properties in relation to Staphylococcus aureus, Bacillus cereus, Escherichia coli and Candida albicans. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates how surfactants affect the in-vitro anti-infective efficacy of micafungin, caspofungin, anidulafungin, and amphotericin B in treating pulmonary mycoses. Methods: MIC values for antifungal agents were determined against Candida krusei (now Pichia kudriavzevii) ATCC 6258, Candida albicans ATCC 90028, and 18 clinical isolates using the broth microdilution method in RPMI medium, following EUCAST recommendations. MIC assays included testing with and without Curosurf® surfactant at 1 mg/mL for C. krusei ATCC 6258 and all C. krusei isolates. Subsequent Time-kill studies in Sabouraud broth involved testing both C. albicans ATCC 90028 and C. krusei ATCC 6258 strains at concentrations equal their respective MIC values, with and without surfactant, using all four antifungals. CFU/mL were assessed at multiple time points up to 24 h. TKCs with different surfactant concentrations for C. krusei ATCC 6258 and mini-TKCs at various concentrations relative to the MIC of C. krusei isolates and the reference strain were conducted with micafungin, anidulafungin, and caspofungin. Results: MIC results showed that 1 µg/mL surfactant reduced killing of micafungin and anidulafungin against C. krusei, while caspofungin was unaffected. Amphotericin B's MIC decreased by half. TKCs demonstrated significant effects of surfactant on micafungin and anidulafungin against C. krusei, with complete abolition of anidulafungin's activity against C. albicans. Conclusion: This in-vitro study highlights the concentration-dependent inhibitory effect of surfactant on antifungal activity against C. krusei and, to some extent, C. albicans, necessitating further clinical validation for invasive lung mycoses treatment. [ABSTRACT FROM AUTHOR]

Context: The controlled slow evaporation process conducted at room temperature has produced a novel hybrid material denoted as (2-hydroxyethyl) trimethylammonium dihydrogen phosphate [2-HDETDHP] (C5H14NO+, H2PO4−), synthesized through the solution growth method. X-ray crystallography analysis reveals a triclinic structure with a filling rate of P and a Z value of 2. This hybrid material displays noteworthy absorption characteristics in the middle and far ultraviolet regions. UV-visible spectroscopy further establishes its transparency in the visible and near-visible ultraviolet domains. FT-IR spectroscopy examines various vibration modes, elucidating their relationships with the functional groups within the structure. Two- and three-dimensional fingerprint maps, coupled with three-dimensional crystal structures through Hirshfeld Surface Analysis, unveil the dominance of O•••H and H•••H interactions in the structure, comprising 49.40% and 50.40%, respectively. Fingerprint plots derived from the Hirshfeld surface assess the percentages of hydrogen bonding interactions, with 80.6% attributed to a fragment patch. The experiment of antimicrobial efficacy of a synthesized product, conducted in triplicate, demonstrated the synthesized product's potential antimicrobial activity. Methods: Hirshfeld surfaces are employed to investigate intermolecular hydrogen bonding, specifically within single phosphate groups. The molecular structure of 2-HDETDHP was refined using single-crystal X-ray analysis, while its optical characteristics were examined through UV-visible spectroscopy. FT-IR spectroscopy is employed for the assignment of molecular vibrations of functional groups in the affined structure. Quantum calculations were executed with the GAUSSIAN 09 software package at B3LYP/6-311G level of theory, to optimize the molecular geometries. The antimicrobial efficacy of a synthesized product was evaluated using the disc diffusion method against antibiotic-resistant Candida albicans, Candida tropicalis, Aspergillus niger, Staphylococcus aureus, and Escherichia coli. Microorganisms were cultured on nutrient agar, and inhibition zones were measured after incubation, with streptomycin and amphotericin as positive controls. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO2) is a well-known material for its biomedical applications, among which its implementation as a photosensitizer in photodynamic therapy has attracted considerable interest due to its photocatalytic properties, biocompatibility, high chemical stability, and low toxicity. However, the photoactivation of TiO2 requires ultraviolet light, which may lead to cell mutation and consequently cancer. To address these challenges, recent research has focused on the incorporation of metal dopants into the TiO2 lattice to shift the band gap to lower energies by introducing allowed energy states within the band gap, thus ensuring the harnessing of visible light. This study presents the synthesis, characterization, and application of TiO2 nanoparticles (NPs) in their undoped, doped, and co-doped forms for antimicrobial photodynamic therapy (APDT) against Candida albicans. Blue light with a wavelength of 450 nm was used, with doses ranging from 20 to 60 J/cm2 and an NP concentration of 500 µg/ml. It was observed that doping TiO2 with Cu, Fe, Ag ions, and co-doping Cu:Fe into the TiO2 nanostructure enhanced the visible light photoactivity of TiO2 NPs. Experimental studies were done to investigate the effects of different ions doped into the TiO2 crystal lattice on their structural, optical, morphological, and chemical composition for APDT applications. In particular, Ag-doped TiO2 emerged as the best candidate, achieving 90–100% eradication of C. albicans. [ABSTRACT FROM AUTHOR]

Candida species is the causative agent in approximately 80% of invasive mycoses and drug-resistant Candida albicans is among the four strains of 'critical priority group' framed by WHO. Lichens are endowed with some rare phytochemicals and a plethora of therapeutics viz. antifungal capacities of Roccella montagnei. Biosynthesis of silver nanoparticles (AgNPs) using lichen could offer an eco-friendly, and cost-effective alternative against emerging 'microbial resistance.' Therefore, the objective was to biosynthesize silver nanoparticles (Rm-AgNPs) using a Hydro-alcoholic (1:1) extract of R. montagnei to develop a potent anticandidal agent against Fluconazole-resistant C. albicans NBC099. UV-Spectroscopy identified AgNPs specific-peak of Rm-AgNPs at 420–440 nm and FTIR revealed the presence of amines, alcohol, aromatic compounds, and acids. SEM and TEM analysis indicated that Rm-AgNPs are spherical shaped with a size range of 10–50 nm. Zetasizer analysis indicated that particles are highly stable and have a mean hydrodynamic diameter of 116 nm with a zeta potential charge of − 41 mV. XRD analysis suggested face centered cubic crystal lattice structure. Results indicated that Rm-AgNPs strongly inhibited the growth of NBC099 at a minimum inhibitory concentration (IC50) of ≤ 15 µg. C. albicans culture treated with Rm-AgNPs at concentrations below IC50, down-regulates the production of different virulence factors in NBC099, viz. hyphal formation (> 85%), biofilms production (> 80%), phospholipase, esterase, proteinase activity. The apoptosis assay demonstrated the Rm-AgNPs induced apoptosis in NBC099 cells via oxidative stress. Interestingly, Rm-AgNPs showed negligible cytotoxicity (< 6%) in murine RAW 246.7 macrophage cells at a concentration above 15 µg/mL. Therefore, Rm-AgNPs have been offered as an anti-candida alternative that can be utilized to improve the efficacy of already available medications. [ABSTRACT FROM AUTHOR]

The escalating prevalence of membrane drug transporters and drug efflux pumps in pathogenic yeast like Candida albicans necessitates a comprehensive understanding of their roles in MDR. The overexpression of drug transporter families, ABC and MFS, implicated in MDR through drug efflux and poses a significant challenge in the diagnosis and treatment of fungal infection. Various mechanisms have been proposed for MDR; however, the upregulation of ABC and MFS superfamily transporters is most noticeable in MDR. The direct inhibition of these transporters seems an efficient strategy to overcome this problem. The goal of the article is to present an overview of the prospect of utilizing these modulators of C. albicans drug transports as effective antifungal molecules against MDR addressing a critical gap in the field. The review tries to address to prevent drug extrusion by modulating the expression of drug transporters of C. albicans. The review discussed the progress in identifying potent, selective, and non-toxic modulators of these transporters to develop some effective antifungals and overcome MDR. We reviewed major studies in this area and found that recent work has shifted toward the exploration of natural compounds as potential modulators to restore drug sensitivity in MDR fungal cells. The focus of this review is to survey and interpret current research information on modulators of C. albicans drug transporters from natural sources emphasizing those compounds that are potent antifungal agents. [ABSTRACT FROM AUTHOR]

Strategies against the opportunistic fungal pathogen Candida albicans based on probiotic microorganisms represent a promising alternative to traditional antifungals. Here, we investigated the effects of Lactobacillaceae isolates from fermented foods or the human vagina, alone or in combination with the probiotic yeast Saccharomyces cerevisiae CNCM I-3856, against C. albicans in vitro. Nine out of nineteen tested strains of Lactobacillaceae inhibited growth of C. albicans with inhibition zones of 1–3 mm in spot assays. Five out of nineteen lactobacilli tested as such or in combination with S. cerevisiae CNCM I-3856 also significantly inhibited C. albicans hyphae formation, including Limosilactobacillus fermentum LS4 and L. fermentum LS5 resulting in respectively 62% and 78% hyphae inhibition compared to the control. Thirteen of the tested nineteen lactobacilli aggregated with the yeast form of C. albicans, with Lactiplantibacillus carotarum AMBF275 showing the strongest aggregation. The aggregation was enhanced when lactobacilli were combined with S. cerevisiae CNCM I-3856. No significant antagonistic effects were observed between the tested lactobacilli and S. cerevisiae CNCM I-3856. The multifactorial activity of Lactobacillaceae strains alone or combined with the probiotic S. cerevisiae CNCM I-3856 against C. albicans without antagonistic effects between the beneficial strains, paves the way for developing consortium probiotics for in vivo applications. [ABSTRACT FROM AUTHOR]

Phage-antibiotic combinations to treat bacterial infections are gaining increased attention due to the synergistic effects often observed when applying both components together. Most studies however focus on a single pathogen, although in many clinical cases multiple species are present at the site of infection. The aim of this study was to investigate the anti-biofilm activity of phage-antibiotic/antifungal combinations on single- and dual-species biofilms formed by P. aeruginosa and the fungal pathogen Candida albicans. The Pseudomonas phage Motto in combination with ciprofloxacin had significant anti-biofilm activity. We then compared biofilms formed by P. aeruginosa alone with the dual-species biofilms formed by bacteria and C. albicans. Here, we found that the phage together with the antifungal fluconazole was active against 6-h-old dual-species biofilms but showed only negligible activity against 24-h-old biofilms. This study lays the first foundation for potential therapeutic approaches to treat co-infections caused by bacteria and fungi using phage-antibiotic combinations. [ABSTRACT FROM AUTHOR]

Coumarins are heterocycles of great interest in the development of valuable active structures in chemistry and biological domains. The ability of coumarins to inhibit biofilm formation of Gram positive bacterium (Staphylococcus aureus), Gram negative bacterium (Escherichia coli) as well as the methicillin-resistant S. aureus (MRSA) has been previously described. In the present work, new hybrid coumarin-heterocycles have been synthesized via the reaction of coumarin-6-sulfonyl chloride and 6-aminocoumarin with different small heterocycle moieties. The biological efficacy of the new compounds was evaluated towards their ability to inhibit biofilm formation and their anti-inflammatory properties. The antimicrobial activities of the newly synthesized compounds were tested against Gram positive bacterium (S. aureus ATCC 6538), Gram negative bacterium (E. coli ATCC 25922), yeast (Candida albicans ATCC 10231) and the fungus (Aspergillus niger NRRL-A326). Compounds 4d, 4e, 4f, 6a and 9 showed significant MIC and MBC values against S. aureus, E. coli, C. albicans, and methicillin-resistant S. aureus (MRSA) with especial incidence on compound 9 which surpasses all the other compounds giving MIC and MBC values of (4.88 and 9.76 µg/mL for S. aureus), (78.13 and 312.5 µg/mL for E. coli), (9.77 and 78.13 µg/mL for C. albicans), and (39.06 and 76.7 µg/mL for MRSA), respectively. With reference to the antibiofilm activity, compound 9 exhibited potent antibiofilm activity with IC50 of 60, 133.32, and 19.67 µg/mL against S. aureus, E. coli, and MRSA, (respectively) considering the reference drug (neomycin). Out of all studied compounds, the anti-inflammatory results indicated that compound 4d effectively inhibited nitric oxide production in lipopolysaccharide-(LPS-) stimulated RAW264.7 macrophage cells, giving NO% inhibition of 70% compared to Sulindac (55.2%) [ABSTRACT FROM AUTHOR]

With the growing resistance of pathogenic microbes to traditional drugs, biogenic silver nanoparticles (SNPs) have recently drawn attention as potent antimicrobial agents. In the present study, SNPs synthesized with the aid of orange (Citrus sinensis) peel were engineered by screening variables affecting their properties via Plackett–Burman design. Among the variables screened (temperature, pH, shaking speed, incubation time, peel extract concentration, AgNO3 concentration and extract/AgNO3 volume ratio), pH was the only variable with significant effect on SNPs synthesis. Therefore, SNPs properties could be enhanced to possess highly regular shape with zeta size of 11.44 nm and zeta potential of − 23.7 mV. SNPs purified, capped and stabilized by cloud point extraction technique were then checked for their antimicrobial activity against Bacillus cereus, Listeria innocua, Listeria monocytogenes, Staphylococcus aureus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhimurium and Candida albicans. The maximum antimicrobial activity of SNPs was recorded against E. coli, L. monocytogenes and C. albicans with clear zone diameter of 33.2, 31.8 and 31.7 mm, respectively. Based on minimum inhibition concentration and minimum bactericidal concentration of SNPs (300 mg/l) as well as their effect on respiratory chain dehydrogenases, cellular sugar leakage, protein leakage and lipid peroxidation of microbial cells, E. coli was the most affected. Scanning electron microscopy, protein banding and DNA fragmentation proved obvious ultrastructural and molecular alterations of E. coli treated with SNPs. Thus, biogenic SNPs with enhanced properties can be synthesized with the aid of Citrus peel; and such engineered nanoparticles can be used as potent antimicrobial drug against E. coli. [ABSTRACT FROM AUTHOR]

Herein, a multifunctional Aspartic-based MOF was designed via a solvothermal route with different cobalt metal precursors such as acetate, sulfate and chloride and designated as LAsp-MOF-Co (–A, –S and –Cl), respectively. The synthesized MOFs were structurally analyzed through FTIR. The morphology exhibited flower-like needle-shaped crystals arranged randomly, and particles agglomerated around the surface. The chemical composition and spectra confirm the metal incorporation in the MOFs. XRD measurements revealed the crystalline nature of the material. The MOF was subjected to catalytic reduction of carcinogenic Methyl Orange and demonstrated excellent efficiency (97%) in reducing the dye with a rate constant of 1.01 min−1. Antimicrobial activity was also performed, and LAsp-MOF-Co (S) showed the best anti-bacterial activity against Staphylococcus aureus (ZOI of 25.0 ± 0.50 mm) and Pseudomonas aeruginosa (ZOI of 27.50 ± 0.25 mm) as well as activity against fungal strain Candida albicans (ZOI 26.00 ± 1.00 mm). The synthesized MOFs can be employed in water treatment infested with microbial strains and dye. [ABSTRACT FROM AUTHOR]

Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aims to examine the antimicrobial properties and washing resistance of cotton fabrics coated with propolis-doped hydrogel. More specifically, we compared the hygienic properties of AgNO3 (a common antimicrobial agent in textile materials), and the antimicrobial properties of propolis for the first time. We used PVA and NaCMC for hydrogel production because they are biocompatible and non-toxic. Later, we looked at how effective the propolis or AgNO3-doped hydrogel-coated cotton fabrics are against gram-positive and gram-negative bacteria and Candida albicans fungus, and compared their findings. Our results demonstrated that propolis could be a natural antibacterial alternative to AgNO3. The more active substance content there was, the more antibacterial and washing resistant it became. We used SEM images of the hydrogel coating and SEM–EDX images to how much silver the silver-doped layers contained. ATR–FTIR results also supported flavonoids and phenol in the structure of propolis itself. The changes in the basic comfort properties of the products were at acceptable levels. [ABSTRACT FROM AUTHOR]

Candida albicans is a commensal fungus that infects the humans and becomes an opportunistic pathogen particularly in immuno-compromised patients. Among the Candida genus, yeast C. albicans is the most frequently incriminated species and is responsible for nearly 50–90% of human candidiasis, with vulvovaginal candidiasis alone, affecting about 75% of the women worldwide. One of the significant virulence traits in C. albicans is its tendency to alternate between the yeast and hyphae morphotypes, accounting for the development of multi-drug resistance in them. Thus, a thorough comprehension of the decision points and genes controlling this transition is necessary, to understand the pathogenicity of this, naturally occurring, pernicious fungus. Additionally, the formation of C. albicans biofilm is yet another pathogenesis trait and a paramount cause of invasive candidiasis. Since 1980 and in 90 s, wide spread use of immune-suppressing therapies and over prescription of fluconazole, a drug used to treat chronic fungal infections, triggered the emergence of novel anti-fungal drug development. Thus, this review thoroughly elucidates the diseases associated with C. albicans infection as well as the anti-fungal resistance mechanism associated with them and identifies the emerging therapeutic agents, along with a rigorous discussion regarding the future strategies that can possibly be adopted for the cure of this deleterious pathogen. [ABSTRACT FROM AUTHOR]

In heterocyclic chemistry, benzimidazole is recognized as a "privileged structure" due to its association with a wide range of biological activities. In this present research work, we included the synthesis, characterization and biological evaluation of substituted derivatives. The designated derivatives were synthesized by the condensation method. ortho-Phenylenediamine was used as the starting material. The designated benzimidazole derivatives were synthesized using different acids and aldehydes. Further, the in-vitro antifungal-activity-synthesized compounds were evaluated against Candida albicans using the agar well diffusion method and the culture tube method. It was concluded that all the designated derivatives of benzimidazole exhibited prominent antifungal activity and can be considered as potent leads in future antifungal research. [ABSTRACT FROM AUTHOR]