Candida Albicans Strains Research Articles

Effect of silver ion and silicate group on the antibacterial and antifungal properties of nanosized hydroxyapatite

Hydroxyapatite is one of the most widely used materials in biomedical applications in reparative and regenerative medicine. Doping of nanosized hydroxyapatite improves its bioactive properties, and thus, the synthesis of different types of nanohydroxyapatite with antimicrobial activity is a perspective route of modern materials science. In this study, undoped hydroxyapatite (HAp), hydroxyapatite doped with silver (HAp with 0.1, 0.5 and 1 mol% Ag+ ions), and silicate-substituted hydroxyapatite doped with silver (Si-HAp with 0.1, 0.5 and 1 mol% Ag+ ions) nanoparticles (NPs) were synthesized by microwave-assisted hydrothermal technique and sintered at 450 °C. The structural properties and composition of obtained hydroxyapatite NPs were investigated using X-ray powder diffraction (XRPD), Fourier-transformed infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The morphology of synthesized nanosized powders was detected using the high-resolution transmission electron microscopy (HRTEM) technique. The results of XRPD for all synthesized nanosized powders confirmed the presence of hydroxyapatite crystal structure. The FT-IR spectra confirmed the presence of functional groups characteristic of the hydroxyapatite structure. The EDS analysis of obtained materials has shown the presence of Ca, P, O, Si, and Ag elements. Significant differences in size and morphology of the obtained particles were found using HRTEM. The particles have an elongated, rod-like shape with subtle differences. Moreover, HAp doped with 1 mol% Ag+ ions and Si-HAp doped with 1 mol% Ag+ ions nanosized powders showed antibacterial activity in comparison to pure hydroxyapatite both against gram-positive and gram-negative bacterial strains (Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis). These two types of hydroxyapatite NPs also demonstrated antifungal activity against reference strains of Candida albicans, Candida kruzei, and Candida tropicalis, with stronger activity observed for Si-HAp doped with silver.

Polysaccharide biocomposites with tunable adsorption and antipathogen activity via surface immobilization of chitosan onto modified flax fibers

Flax fiber modified composite (FFMC) duplex systems with unique sorbent and antipathogen properties were developed by physisorption of chitosan onto modified flax fibers by a facile method. Complementary characterization of the FFMCs (Raman, NMR, and IR, SEM, XRD, TGA and BET analysis) revealed variable composite morphology with incremental chitosan doping and supramolecular interactions between the fiber substrate and immobilized chitosan. Dye adsorption profiles of FFMCs with Rose Bengal corroborated the role of physisorption with an adsorption capacity that rises to 17.9 mg/g, whereas the water sorption capacity reaches an impressive value ca. 11 g/g, which indicated the role of synergism upon chitosan immobilization. Anti-microbial and fungal properties were supported by antimicrobial tests. The FFMCs have high antimicrobial potency toward gram negative (E. coli), gram positive (Streptococcus aureus) and a fungal strain (Candida albicans) based on the low FFMC dosages required to achieve 100 % microbial elimination. This versatile class of unique biocomposites displayed unique structure-function relationships related to synergistic water sorption and antipathogenic effects, as compared to available literature reports. FFMCs are a diversiform class of biocomposites with unique physicochemical and biological properties that extend the field of adsorption science and technology from environmental remediation to biomedical devices.

The Neosartorya (Aspergillus) fischeri antifungal protein NFAP2 has low potential to trigger resistance development in Candida albicans in vitro.

Due to the increase in the number of drug-resistant Candida albicans strains, new antifungal compounds with limited potential for the development of resistance are urgently needed. NFAP2, an antifungal protein (AFP) secreted by Neosartorya (Aspergillus) fischeri, is a promising candidate. We investigated the ability of C. albicans to develop resistance to NFAP2 in a microevolution experiment compared with generic fluconazole (FLC). C. albicans adapted to only 1× minimum inhibitory concentration (MIC) of NFAP2, which can be considered tolerance rather than resistance, compared with 32× MIC of FLC. Genome analysis revealed non-silent mutations in only two genes in NFAP2-tolerant strains and in several genes in FLC-resistant strains. Tolerance development to NFAP2 did not influence cell morphology. The susceptibility of NFAP2-tolerant strains did not change to FLC, amphotericin B, micafungin, and terbinafine. These strains did not show altered susceptibility to AFPs from Penicillium chrysogenum, except one which had less susceptibility to Penicillium chrysogenum antifungal protein B. FLC-resistant strains had decreased susceptibility to terbinafine and NFAP2, but not to other drugs and AFPs from P. chrysogenum. NFAP2-tolerant and FLC-resistant strains showed decreased and increased NFAP2 binding and uptake, respectively. The development of tolerance to NFAP2 decreased tolerance to cell wall, heat, and UV stresses. The development of FLC resistance increased tolerance to cell wall stress and decreased tolerance to heat and UV stresses. Tolerance to NFAP2 did not have significant metabolic fitness cost and could not increase virulence, compared with resistance to FLC.IMPORTANCEDue to the increasing number of (multi)drug-resistant strains, only a few effective antifungal drugs are available to treat infections caused by opportunistic Candida species. Therefore, the incidence of hard-to-treat candidiasis has increased dramatically in the past decade, and the demand to identify antifungal compounds with minimal potential to trigger resistance is substantial. The features of NFAP2 make it a promising candidate for the topical treatment of Candida infection. Data on the development of resistance to antifungal proteins in Candida albicans are lacking. In this study, we provide evidence that NFAP2 has a low potential to trigger resistance in C. albicans in vitro, and the developed tolerance to NFAP2 is not associated with severe phenotypic changes compared with development of resistance to generic fluconazole. These results suggest the slow emergence of NFAP2-resistant Candida strains, and NFAP2 can reliably be used long-term in the clinic.

Novel Liposome-Gel Formulations Containing a Next Generation Postbiotic: Characterization, Rheological, Stability, Release Kinetic, and In Vitro Antimicrobial Activity Studies.

In recent years, in addition to the positive effects of probiotics and prebiotics on health, increasing research has shown that postbiotics also have significant potential in the health field. Postbiotics are bioactive components produced by probiotic bacteria during fermentation and may exhibit antimicrobial activity. This study investigated the antimicrobial effects of liposomal postbiotics formulated in gel. Various postbiotic-containing liposomal systems have been developed and optimized to prepare formulations. Optimized liposomes and liposomal postbiotic-containing gel forms were examined in terms of particle size, polydispersity index, zeta potential, structural properties, encapsulation efficiency, permeability, release profiles, and stability. Finally, the antimicrobial activities of the postbiotics and the optimum gel formulation LG1 were evaluated on Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Enterococcus hirae, and Candida albicans strains using disk diffusion and microdilution methods. The optimum liposome formulation L1 was determined to have a particle size of 185.32 ± 0.80 nm, a polydispersity index of 0.206 ± 0.012, a zeta potential of 35.0 ± 0.5 mV, and an encapsulation efficiency of 17.52%. Its permeability was determined as 51.52% at the end of 6 h. In vitro release studies showed that the drug release profile was in accordance with first-order kinetics and suitable for controlled release. The findings show that formulated postbiotics have similar antimicrobial activity to free postbiotics. These results suggest that liposomal gel formulations support the antimicrobial effects of postbiotics while providing advantages of use. In conclusion, the findings contribute to a better understanding of the antimicrobial potential of postbiotics and lipogelosomal postbiotics and optimize their use in pharmaceutical applications.

Illustration of the Distribution of DNA Sequences and Their Frequencies Within the MEP2 Gene Across Ten Candida Species

Candida species have an impact on human skin health and occasionally can lead to catastrophic conditions, such as skin cancer. The nitrogen supply in growth media regulates MEP2 gene expression. MEP2 protein may regulate the amount of ammonium accessible to cells by directly affecting ammonium assimilation. Reducing MEP2 expression removed its potential to drive filamentous growth.This study aimed to examine serial imaging of the MEP2 gene with chaos game representation (CGR) and frequency chaos game representation (FCGR). In addition, the effect of mutations in Candida albicans strains on MEP2 docking with lauramine oxide (LDAO) was investigated. The MEP2 gene was selected for 10 Candida species from the National Center for Biotechnology Information to compare DNA sequences using conventional and portray methods (CGR and FCGR). The molecular docking between MEP2 and LDAO was determined using the HDOCK server.CGR findings revealed that Candida margitis, Candida orthopsilosis, Candida dubliniensis, Candida theae, and C albicans had approximately 65% of the same characteristics. According to FCGR, there was a 75% similarity between C albicans, C theae, C dubliniensis, C orthopsilosis, and C margitis. In certain strains, but not all a mutation in the conserved region of the protein caused a change in the docking residue of LDAO with MEP2.The CGR and FCGR protocols are considered practical and reliable tools for identifying protein and DNA sequence similarities. Approximately 80% of the existing algorithms for determining multiple sequence alignments are similar to traditional methods. Targeted treatment will be possible as determining MEP2 mutations is crucial for using Candida as a nitrogen source.

Blood cultures contain populations of genetically diverse Candida albicans strains that may differ in echinocandin tolerance and virulence.

It is unknown whether within-patient Candida albicans diversity is common during bloodstream infections (BSIs). We determined whole genome sequences of 10 C. albicans strains from blood cultures (BCs) in each of 4 patients. BCs in 3 patients contained mixed populations of strains that differed by large-scale genetic variants, including chromosome (Chr) 5 or 7 aneuploidy ( n =2) and Chr1 loss of heterozygosity ( n =1). Chr7 trisomy (Tri7) strains from patient MN were attenuated for hyphal and biofilm formation in vitro compared to euploid strains, due at least in part to NRG1 over-expression. Nevertheless, representative Tri7 strain M1 underwent filamentation during disseminated candidiasis (DC) in mice. M1 was more fit than euploid strain M2 during DC and mouse gastrointestinal colonization, and in blood ex vivo. M1 and M2 exhibited identical echinocandin minimum inhibitory concentrations, but M2 was more tolerant to micafungin in vitro. Furthermore, M2 was more competitive with M1 in mouse kidneys following micafungin treatment than it was in absence of micafungin. Tri7 strains represented 74% of patient MN's baseline BC population, but after 1d and 3d of echinocandin treatment, euploid strains were 93% and 98% of the BC population, respectively. Findings suggest that echinocandin tolerant, euploid strains were a subpopulation to more virulent Tri7 strains at baseline and then were selected upon echinocandin exposure. In conclusion, BCs in at least some patients are comprised of diverse C. albicans populations not recognized by the clinical lab, rather than single strains. Clinical relevance of C. albicans diversity and antifungal tolerance merits further investigation.

Evaluation of Antifungal Activity of Psidium guajava (Guava) Leaf Extracts

Aims: This study aimed to evaluate the effectiveness of four Psidium guajava leaf extracts against three strains of Candida albicans and a strain of Cryptococcus neoformans. Study Design: Experiment-observational study. Place and Duration of Study: P. guajava leaves were collected from specific areas in Regions Three and Four in Guyana; and the preparation of the leaf extracts and the treatment against the fungi were performed in two laboratories at the University of Guyana from August 2022-September 2023. Methodology: P. guajava leaves were washed with water, air-dried at room temperature, and ground in a disinfected food mixer. Extracts were prepared by soaking the ground leaves in different solvents, and then using the rotary evaporator to reduce the solutions and obtain crude extracts. Filter paper discs were prepared and allowed to soak in various concentrations of the crude extracts. The discs were then subjected to antifungal susceptibility testing on Potato Dextrose agar seeded with an appropriate fungus according to Clinical Laboratory Standards Institutes guidelines. The plates were incubated and the zone of inhibition (ZOIs) was measured. Results: P. guajava leaves were effective against all four strains of fungi evaluated. The largest ZOI was observed for C. neoformans (25 mm) with the ethyl acetate extract at 100 mg/mL concentration. Large ZOI was also observed for the three strains of C. albicans (10-15 mm). For one of the C. albicans strains, a ZOI significantly higher than the antifungal agents (ketoconazole and fluconazole) was observed with the P. guajava ethyl acetate extract at 100 mg/mL. Conclusion: It can be concluded that P. guajava leaves have antifungal activity against C. albicans and C. neoformans, potentially greater than current antifungal agents like ketoconazole and fluconazole.

Inhibition of Virulence Associated Traits by β-Sitosterol Isolated from Hibiscus rosa-sinensis Flowers Against Candida albicans: Mechanistic Insight and Molecular Docking Studies.

The emerging drug resistance and lack of safer and more potent antifungal agents make Candida infections another hot topic in the healthcare system. At the same time, the potential of plant products in developing novel antifungal drugs is also in the limelight. Considering these facts, we have investigated the different extracts of the flowers of Hibiscus rosa-sinensis of the Malvaceae family for their antifungal efficacy against five different pathogenic Candida strains. Among the various extracts, the chloroform extract showed the maximum zone of inhibition (26.6 ± 0.5mm) against the Candida albicans strain. Furthermore, the chloroform fraction was isolated, and a sterol compound was identified as β-sitosterol. Mechanistic studies were conducted to understand the mechanism of action, and the results showed that β-sitosterol has significant antifungal activity and is capable of interrupting biofilm formation and acts by inhibiting ergosterol biosynthesis in Candida albicans cells. Microscopic and molecular docking studies confirmed these findings. Overall, the study validates the antifungal efficacy of Candida albicans due to the presence of β-sitosterol which can act as an effective constituent for antifungal drug development individually or in combination.

Candida albicans infection model in Drosophila melanogaster suggests a strain-specific virulent factor boosting a stormy innate immune response.

Pathogens drive the evolution of host defence strategies, with both innate and adaptive immune systems playing key roles. Priming enhances the innate immune system's readiness by functionally reprogramming immune cells after initial exposure to stimuli, like β-glucans. In this sense, Drosophila melanogaster is a valuable model to evaluate the role of innate immunity to control infections. In this study we aimed to set light on the immune priming effect of oral treatment with heat-killed M. manresensis and two different heat-killed C. albicans isolates upon systemic infection by C. albicans in the D. melanogaster model. A clinical and a control ATCC 90028 Candida albicans strain were used. Flies were primed through oral administration of heat-killed C. albicans (hkCa), both clinical and control, and hk-Mycolicibacterium manresensis. After priming, flies were systemically infected with both C. albicans isolates. Host survival, pathogen load, and immune response in response to treatment and infection were evaluated. Both treatments showed a significant capacity to enhance the expression of antimicrobial peptides, in particular Diptericin, and Drosomycin in males. This response had a marked sexual dimorphism due to the difference in Upd3, Nox, and Duox expression. Surprisingly, even when priming was able to avoid the growth of both C. albicans strains, survival was not improved in the case of the clinical isolate, causing an unexpected mortality rate in hours, regardless of the host's sex. Gene expression analysis 24 hours post-infection showed an exacerbated increase in Diptericin, Drosomycin and Upd3 expression upon infection with the clinical strain. Data herein suggests the presence of a strain-specific component in C. albicans as the booster of a "stormy" innate immune response, which must be further investigated, and position D. melanogaster as a useful model for evaluating virulent factors related to the modulation of the innate immunity.

Evaluation of Emulsification Techniques to Optimize the Properties of Chalcone Nanoemulsions for Antifungal Applications.

Background/Objectives: Nanoemulsions (NEs) possess properties that enhance the solubility, bioavailability and therapeutic efficacy of drugs. Chalcones are compounds known for their antifungal properties. In this study, we evaluated different emulsification techniques to create alginate nanoemulsions containing chalcone (1E,4E)-1,5-bis (4-methoxyphenyl) penta-1,4-dien-3-one (DB4OCH3). Our goal was to develop an antifungal formulation targeting Candida albicans strains. Methods: Ultrasound and ultrasound combined with high-speed homogenization techniques were used to prepare alginate-stabilized nanoemulsions. Particle size, zeta potential and encapsulation efficiency were evaluated. Additionally, in vitro release studies were conducted. Results: The combined emulsification technique produced stable nanoparticles with high encapsulation efficiency and antifungal activity, with a minimum inhibitory concentration of 8.75 μg/mL for the nanoemulsions compared to 312 µg/mL for free DB4OCH3. NEs' effectiveness can be attributed to their ability to form nanodroplets efficiently, facilitating the solubilization of the chalcone in the oily phase. The particle size varied between 195.70 ± 2.69 and 243.40 ± 4.49 nm, with an increase in chalcone concentration leading to larger particle sizes. The zeta potential showed values from -91.77 ± 5.58 to -76.90 ± 4.44 mV. The UHS-7 sample exhibited an encapsulation efficiency of 92.10% ± 0.77, with a controlled in vitro release of 83% after 34 h. Molecular docking simulations showed that the aromatic nature of DB4OCH3 resulted in the formation of apolar interactions with aromatic residues located in the active site of the TMK, as observed in their respective co-crystallized inhibitors, within an affinity energy range that enables optimum specificity of the ligand for these two pathways. Pharmacokinetic analyses indicated high passive cell permeability and low hepatic clearance, and phase I metabolism reduces its oral bioavailability and metabolic stability, suggesting a promising active ingredient as an oral drug with control of the daily oral dose administered. Conclusions: The combined nanoemulsification technique led to the formation of finely dispersed nanodroplets that favored the solubilization of the chalcone in the oil phase, which led to a better performance in the antifungal properties. DB4OCH3 shows promise as an oral drug with controlled dosing.

Biological Potential of Asphodelus microcarpus Extracts: α-Glucosidase and Antibiofilm Activities In Vitro.

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of Candida spp. in areas like the mouth and genitalia. Asphodelus microcarpus contains bioactive flavonoids with potential enzyme inhibitory properties. This study investigates α-amylase and α-glucosidase inhibitory activities and antioxidant and antimycotic capacity of ethanolic extracts from different parts of A. microcarpus. Results show that extracts significantly inhibit α-glucosidase, with the IC50 value being up to 25 times higher than for acarbose, while exerting low α-amylase activity. The extracts also demonstrated strong antioxidant properties and low cytotoxicity. The presence of phenolic compounds is likely responsible for the observed biological activities. Molecular docking analysis of 11 selected compounds identified emodin and luteolin as significant inhibitors of α-glucosidase. Additionally, the extracts demonstrated significant antibiofilm action against an MDR strain of Candida albicans. These findings suggest that A. microcarpus is a promising source of natural compounds for T2D management.

Evaluation of Antimicrobial, Antitumor, Antioxidant Activities, and Molecular Docking Studies of Some Co(II), Cu(II), Mn(II), Ni(II), Pd(II), and Pt(II) Complexes With a Schiff Base Derived From 2‐Chloro‐5‐(trifluoromethyl)aniline

ABSTRACTThe antimicrobial, antitumor and antioxidant potential of Co(II), Cu(II), Mn(II), Ni(II), Pd(II), and Pt(II) complexes with 2‐(((2‐chloro‐5‐(trifluoromethyl)phenyl)imino)methyl)phenol HL ligand was investigated. A molecular docking study was carried out to estimate the predicted binding affinity of the compounds to protein targets involved in proliferative and bacterial activities. Fluorescence quenching studies and synchronous spectra were used to examine the metal complexes interactions with CT‐DNA and BSA protein. The DNA binding study have revealed that the complexes are capable of binding with DNA via intercalative mode. The antimicrobial activity of the ligand and metal complexes was studied against three Gram‐positive bacteria, two Gram‐negative bacteria, and three strains of fungi. The best antibacterial effect was demonstrated by the Pt(II) complex on the Staphylococcus aureus strain, and as for the inhibitory effect on fungi, it was stronger on the Candida albicans strain after treatment with the Co(II) complex. The in vitro antiproliferative activity of ligand and complexes was analyzed using MTT, Annexin V/PI, and cell cycle assays. The in vitro results showed that, except for Pd(II) complex, where slight effects were observed, the MCF‐7 line was resistant to the activity of the complexes. In the case of A549 cells, Cu(II) and Pd(II) complexes showed a dose‐dependent antitumor activity, confirmed by both the Alamar blue and the Annexin V/PI analysis. Finally, the antioxidant activity of the compounds was examined by ABTS and DPPH methods. Antioxidant investigation showed that the Ni(II) complex possesses a remarkable ability to trap the cation of the ABTS+ radical (IC50 value 9.35 μM).

Acetic Acid-Driven One-Pot Synthesis of 4,7-dihydro-[1,2,3]thiadiazolo[5,4-b]pyridine-6-carboxamides and Pharmacological Evaluations.

A diverse set of 4,7-dihydro-[1,2,3]thiadiazolo[5,4-b]pyridine-6-carboxamides 4(a-o) was synthesized via a one-pot reaction of 5-amino-[1,2,3]thiadiazole, various aromatic aldehydes, and different acetoacetanilides, using glacial acetic acid. The resulting compounds were obtained in moderate to good yields. All the newly synthesized compounds were evaluated for their antimicrobial activity. Among them, compound 4 e demonstrated superior efficacy against the Salinivibrio proteolyticus strain of Gram-negative bacteria compared to ciprofloxacin. Compound 4 d exhibited the highest potency against the fungal strain Candida albicans, surpassing amphotericin B. The physicochemical characteristics of 4 d and 4 e were assessed. According to docking analysis, DHTDAPy 4 e shows a higher binding affinity of -7.2 kcal/mol in the binding cavity of the receptor. These findings illustrate the safety, tolerability, and potency of the newly synthesized DHTDAPy compounds against fungal and bacterial infections.

Antimicrobial Activity of Honey and Propolis from Alba County, Romania.

Investigating the quality of bee products obtained across different geographical regions and analyzing their antimicrobial activity is of significant interest to various scientific disciplines. This study focuses on comparing the antimicrobial activity of honey and propolis samples from different areas of Alba County, Romania. The quality parameters of five samples of two types of bee products (honey and propolis) were assessed. Then, the samples were tested to comparatively determine their antimicrobial properties against 12 species of bacteria (Escherichia coli, Salmonella typhimurium, Salmonella enteritidis, Salmonella anatum, Salmonella choleraesuis, Pseudomonas aeruginosa, Pseudomonas fluorescens, Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Bacillus subtilis, and Listeria monocytogenes) and 7 fungal strains (Candida albicans, Aspergillus niger, Aspergillus flavus, Penicillium chrysogenum, Rhizopus stolonifer, Fusarium oxysporum, and Alternaria alternata). Of the bacterial strains, the most sensitive to the action of honey samples were the two strains of Staphylococcus followed by P. fluorescens. The two strains of Pseudomonas and L. monocytogenes were the most sensitive to the activity of propolis. Of the fungal strains, F. oxysporum was the most sensitive to the actions of both honey and propolis, followed by P. chrysogenum in the case of honey samples and the two Aspergillus strains in the case of propolis. These findings indicate that bee products are rich sources of bioactive compounds exhibiting strong antimicrobial properties and significant potential for the development of new phytopharmaceutical products.

The Antifungal Effects of Hypericum perforatum Nanoemulsion against Candida albicans

Background Oral stomatitis is one of the common infections related to dentures (complete or partial), which is seen in the form of diffuse inflammation, mainly with Candida albicans. The aim of the present study was to investigate the antifungal effects of Hypericum perforatum nanoemulsion against Candida albicans. Materials and Methods The microdilution technique has been used in order to determine the antifungal effects of Hypericum perforatum nanoemulsion. The study has involved four groups: Hypericum perforatum oil, Hypericum perforatum nanoemulsion, distilled water as a negative control, and nystatin as a positive control. The first concentration of nanoemulsion in which no clear fungal growth was observed in the culture medium has been considered as the Minimum Inhibitory Concentration (MIC) and the first concentration in which the fungal growth was completely stopped and no fungal growth was observed in the culture medium has been considered as the Minimum Fungicide Concentration (MFC). One-way Analysis of Variance (ANOVA) has been employed to compare the results between the groups. Tukey's post-hoc test has been used to make comparisons between the groups. The significance level has been considered at less than 0.05. Results Both Hypericum perforatum oil and Hypericum perforatum nanoemulsion have been found to exhibit good antifungal activity against Candida albicans. The MIC and the MFC of the nanoemulsion form have been found to be lower than the non-nanoemulsion form (P<0.05). Among the studied groups, the nystatin group had been found to have the best effect (P<0.05). Conclusion Considering the different antifungal mechanisms and also the different resistance mechanisms of nystatin and Hypericum perforatum nanoemulsion, the prepared nanoemulsion can be used to treat and reduce the population of nystatin-resistant Candida albicans strain. However, the efficiency of these materials needs to be confirmed in larger studies on resistant strains.

In vitro and silico Analysis of Amentoflavone against Candida albicans with a Competitive Action about Amphotericin B

Introduction: Antifungal resistance is a global health problem, and alternatives for control and treatment must be sought. Thus, substances isolated from plants with antifungal capacity have received considerable attention in the pharmaceutical sector. Ouratea fieldingiana, popularly known as batiputá, is a tree species found in northeastern Brazil, with its leaves rich in biflavonoids such as amentoflavone. Biflavonoids are well-studied due to their high antifungal capacity. Objectives: Carry out the isolation, identification, and characterization of the compound amentoflavone (AMT), as well as evaluate its antifungal activity and modulatory effect against strains of Candida albicans, also including the computational study of the mechanism of action of the compound AMT against the Als3 and Sap5 enzymes of C. albicans. Methodology: Column chromatography was used to isolate the AMT compound from the species O. fieldingiana, and its characterization was performed by high-performance liquid chromatography (HPLC). The antifungal activity was analyzed by the broth microdilution method. Modulatory activity assays were performed by the checkerboard technique using AMT and amphotericin B (AmB) as a standard. For the in silico study, computational simulations of the interaction between the enzymes Als3 and Sap5, and AMT were performed using the Vina AutoDock Code. Results: The AMT compound showed an inhibitory effect against all strains of C. albicans. Regarding modulatory activity, an indifferent and antagonistic effect was observed for all C. albicans strains tested. Molecular docking with AMT showed higher affinity energy for the Als3 and Sap5 enzymes than AmB. The results obtained in this study suggest that AMT has antifungal effects, as well as a high affinity for the Als3 and Sap5 enzymes of C. albicans. Conclusion: These results prove that the AMT compound could be a potential source of a new biotechnological product, acting as a natural antifungal agent.

Antifungal activity’s study of the of new derivatives of pyrrolo[3,4-c]pyrazol-3-ones and pyrazol-3- carboxamides in the biofilm model of Candida spp.

The search for new antifungal drugs is current interest due to the wide spread of fungal infections. To simulate the antifungal effect of new promising compounds with high antifungal activity in planktonic culture in clinical practice, it is necessary to study their effect on the biofilm of micromycetes.Aim: To study the antifungal activity of new promising representatives of silver salts of pyrazoles and their condensed systems under conditions of biofilm formation.Material and Methods. To study the antifungal activity of silver salts I and II, the micromethod of two-fold serial dilutions was used. Activity against a typical and 14 clinical highly virulent isolates of C. albicans was studied. The study of the antimycotic activity of substances under biofilm conditions was carried out using resazurin to quantify the degree of biofilm formation. The minimum inhibitory concentrations for biofilms were calculated (sMIC50 - the concentration of the antifungal substance at which a 50% decrease in fluorescence is observed compared to the positive control).Results and Discussion. It was shown that the antifungal effect of the studied compounds in biofilm culture of clinical strains of Candida spp. is significantly lower than in planktonic culture. High antifungal activity of the silver salt of pyrazole-3- carboxamide in planktonic and biofilm cultures of resistant strains of Candida albicans, exceeding the effect of the reference drug fluconazole by 2.8–11.2 times, was revealed.Conclusion. A promising pyrazole-3-carboxamide derivative has been identified that effectively inhibits the growth of Candida albicans biofilms, which can be recommended for further study.

MICROBIOLOGICAL CHARACTERISTICS OF THE ORAL MUCOSAIN PATIENTS WITH LICHEN PLANUS ERYTHEMATOSUS

Lichen planus is a multifactorial disease that involves immune, neuroendocrine, microbiological, and other metabolic processes associated with skin and mucosal damage. The microflora of the oral cavity in CPL SOPR was studied by E. S. Leontieva etal., 2014, the microbiocenosis of various biotopes of the oral cavity in patients with CPL SOPR was studied. The study involved 95 patients with CPL SOPR, who underwent hygienic, periodontal and microbiological research methods. The results of the degree of bacterial contamination indicate a more pronounced colonization of foci of CPL lesion by representatives of the coccoid flora: Streptococcus salivares and Streptococcus mutans, but there is no correlation between them. Isolated Streptococcus Sanguis colonies were observed in 55% of patients. In addition, fungi of the genus Candida albicans were detected in 50%, the average level of adhesion of Candida albicans strains in patients with CPL was 16.78±1.64%. The frequency of detection of fungi of the genus Candida albicans in foci of CPL lesion correlates (r=0.79) with the activity of the disease course. The significance of Candida albicans contamination is determined not so much by the degree of contamination of the lesion foci, but by such pathogenic properties of Candida albicansas the level of adhesion and the activity of germination tubes formation [1,2,3,6,11,2,3,6,11]. Authors Chuikin S. V., Akmalova G. M., Chernysheva N. D., 2014, analyzed the qualitative and quantitative microbiocenosis of the oral cavity in patients with CPL. The study included 145 patients with CPL aged 21 to 76 years, of whom 5% were men and 95% were women. The predominant form of CPL was erosive-ulcerative form (33.1%), the lowest frequency was observed in 2% of patients with bullous form. The results of the study showed that dysbiotic changes were observed with a predominance of candida infection and were found in 57.2% of the examined patients, which are observed more often in erosive-ulcerative and bullous forms of CPL. The results of the study showed that all the examined patients had microbiocenosis disorders of varying severity from dysbiotic shift to IYgrade IY dysbiosis and high sensitivity to bacteriophages was revealed. It should be noted that high sensitivity of pathogenic and opportunistic microorganisms sown in дисбактериозахoral dysbiosis was detected to цефалоспориногоcephalosporin antibiotics (100%), oxacillin (79%), gentamicin (76%), lincomycin (73%). [5,7,9,12]. A number of foreign authors Villa (TG, Sá ncheznchez-Pérez rez Á, Sieiro C., 2021) believe that microbial infection triggers an autoimmune response. Withdysbiosisof the intestinal microbiota , there is a violationof the integrity of the intestinal barrier, followed by an increase in intestinal permeability, and the penetration микроорганизмof microorganisms and their toxinов into the circulatory system. Current knowledge about this disease requires the inclusion of this disease in the list of autoimmune diseases, since the progression of CPL involves colonization of locally affected areas by bacteria, fungi or viruses that occur after damage to the oral mucosa and skin. The process of healing the disease should include eliminating microbial dysbiosis and restoring the normal microbiota of the oral mucosa, skin, and intestines. [4,6,8,10,13,14].

Candida albicans strains adapted to the mouse gut are resistant to bile salts via a Flo8-dependent mechanism

Candidaalbicans normally colonizes the human gastrointestinal tract as a commensal. Studying fungal factors involved in colonizing the mammalian gastrointestinal tract requires mouse models with altered microbiota. We have obtained strains of C.albicans through microevolution in the mouse gut for a prolonged period (one year) that display a substantial increase in fitness in this niche. These strains show resistance to bile salts, an increase in their adhesion to the intestinal mucosa, and are unable to filament in response to serum. Genetic analysis revealed some alterations, mainly a triploidy of chr7, a whole chr6 homozygosis, and an SNP in the FLO8 gene (located in the chr6), resulting in a truncated protein version. A wild type FLO8 gene complemented filamentation and bile salt sensitivity, but showed an intermediate fitness phenotype in colonization. Alterations in bile salt sensitivity were also evident in bmt mutants, defective in β-mannosylation, and transcriptional targets of Flo8, suggesting a link between the fungal cell wall and mammalian gut colonization via the Flo8 transcriptional regulator.

Antifungal effect of Crescentia cujete fruit extracts on clinical strains of Candida albicans

Candidiasis is a common fungal infection globally, ranging from superficial to severe invasive forms that can be life-threatening. This study aimed to evaluate the antifungal effects of ethanol and n-hexane extracts from Crescentia cujete fruit against Candida albicans strains. Crescentia cujete fruit pulp was dried and extracted using Soxhlet with ethanol and n-hexane. Two reference strains of C. albicans (ATCC 10231 and 90028) and 12 clinical isolates from vaginal smears were tested under various conditions: without extract, with serial dilutions of ethanol or n-hexane extracts, and with ethanol and n-hexane at the same concentrations. Growth was measured using MicroELISA equipment. Results showed that n-hexane and ethanol extracts significantly reduced the growth of 9/12 and 4/12 clinical strains, respectively, and also affected the ATCC 90028 and ATCC 10231 strains. A direct correlation was observed between growth inhibition and extract concentration, with n-hexane exhibiting a stronger correlation (Spearman's Rho=0.609, p<0.05) compared to ethanol (Spearman's Rho=0.387, p<0.05). This study is the first to demonstrate the antifungal effects of Crescentia cujete fruit extracts on clinical Candida albicans strains, suggesting that a low-polarity compound in the fruit inhibits Candida albicans, including the ATCC 1031 strain resistant to common antifungals.