Candida Albicans Strains Research Articles

IN VITRO ASSESSMENT OF ANTIMICROBIAL AND ANTIOXIDANT ACTIVITIES OF EXTRACTS OF YEMENI FAGONIA SCHWEINFURTHII HADIDI

Background: Antioxidant and antimicrobial properties of plant extracts are attributed to bioactive components derived from medicinal plants. This study inspected into the antimicrobial and antioxidant effects of extracts from Fagonia schweinfurthii Hadidi aerial portions. Method: Several solvents, including n-hexane, ethyl acetate, and methanol, were utilized sequentially to extract secondary metabolites from F. schweinfurthii aerial parts. Antimicrobial activity was evaluated using the well diffusion method and broth serial dilution, whilst antioxidant activity was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl radical scavenging method. Results: The findings exposed that the studied fungal strains (Candida albicans and Trichophyton rubrum) were resistant to all plant extracts. F. schweinfurthii methanol and ethyl acetate extracts demonstrated inhibitory effects on Gram-positive and Gram-negative tested bacteria with minimum inhibitory concentration between 2.5 and 20 mg/ml. In addition, the most sensitive bacterium was Proteus vulgaris, with an inhibitory concentration (2.5 and 5 mm). While the most resistant bacterium was Staphylococcus epidermidis. Due to the physical and chemical properties of the solvents, different extracts of F. schweinfurthii aerial parts exhibited diverse antioxidant capabilities in the antioxidant activity experiment. Methanol and ethyl acetate extracts exhibited IC50 values of 236 ± 0.2µg/ml and 359.4± 0.6µg/ml, respectively. Conclusion: According to the findings of this study, the aerial portions of F. schweinfurthii could be considered a possible source of natural antioxidants as well as a valuable source of antibacterial agents against bacteria that cause ear infections. Peer Review History: Received: 5 July 2022; Revised: 20 August; Accepted: 9 September, Available online: 15 September 2022 Academic Editor: Dr. DANIYAN Oluwatoyin Michael, Obafemi Awolowo University, ILE-IFE, Nigeria, toyinpharm@gmail.com UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Ali Jaber, Laboratory for Research and Development of Medicines and Natural Products, RDMPN, Faculty of Pharmacy, Lebanese University, Beirut, Lebanon. Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Similar Articles: INVESTIGATION OF LIPOIDIAL CONTENTS AND THEIR ANTIMICROBIAL ACTIVITY OF FORSSKAOLEA VIRIDIS AND TRICHODESMA EHRENBERGII WILDLY DISTRIBUTED IN EGYPT ANTI-INFLAMMATORY AND ANTI-OXIDANT ACTIVITIES OF METHANOL EXTRACT OF BAPHIA NITIDA

Photocatalytic and antimicrobial activities of pure and Mn doped ZnO nanoparticles synthesised by Annona Muricata leaf extract

ABSTRACT The present work aim to investigate the photocatalytic, antibacterial and antifungal activities of Zn1-xMnxO (x = 0.0, 0.03, 0.05 and 0.07) nanoparticles synthesised using the leaf extract of Annona Muricata via green synthesis method. The effect of Mn doping in the obtained nanopowder were studied by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HRTEM), selected area diffraction pattern (SAED), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDX) and UV-visible spectroscopy techniques. XRD pattern confirms hexagonal wurtzite structure of ZnO nanoparticles. Incorporation of Mn into the ZnO host lattice was confirmed by XPS measurement. Morphology of nanoparticles shows irregular, spherical shapes with agglomeration. Presence of Zn, Mn and O elements in the EDAX reveals the perfect nature of nanostructures. The synthesised pure and Mn-doped ZnO nanoparticles were found to be significant antibacterial activity against gram positive Bacillus subtilis, Staphylococcus aureus and gram negative Pseudomonas aeruginosa bacterial pathogens as well as the fungal strain of Candida albicans and Aspergillus Niger. The minimum zone of inhibition observed for bacterial and fungal pathogens confirms better antimicrobial activity of ZnO nanoparticles. The Mn-doped nanoparticle shows comparatively enhanced removal of methylene blue (MB), malachite green (MG) and Congo red (CR) dye under sunlight. These results indicates the green synthesised pure and Mn-doped ZnO nanoparticles have valuable applications in environmental and biomedical fields.

2-Aminophenol-based ligands and Cu(II) complexes: Synthesis, characterization, X-ray structure, thermal and electrochemical properties, and in vitro biological evaluation, ADMET study and molecular docking simulation

Two ligands 2-[(2,4-dimethoxybenzylidene)amino]phenol (HA), 2-[(2,5-dimethoxybenzylidene)amino]phenol (HB) and their Cu2+ transition metal complexes were synthesized and characterized by elemental analysis, mass spectra, UV–vis, 1H and 13C NMR (only used for HA and HB) and FTIR methods. Single crystals of the ligands HA and HB were obtained from ethanol solution, and single-crystal X-ray diffraction techniques have elucidated their molecular structures. Thermal properties of the 2-amino phenol-based ligands (HA and HB) and their Cu2+ metal complexes have been investigated by using thermogravimetric (TGA) and differential thermal analyses (DTA) methods. The electrochemical properties of all compounds have been studied in the -1.1 to +1.1 V range. In vitro antimicrobial activity was screened against two gram-positive (Staphylococcus aureus and Bacillus cereus), two gram-negative (Escherichia coli and S. typhimurium), and one fungal strain (Candida albicans) and compounds exhibited bactericidal and fungicidal behavior. The cytotoxic properties of the compounds were evaluated on HUVEC and MCF-7 cells by calculating IC50 values for both cell types. The smallest IC50 values ​​of the compounds tested were 34.19 µM for the HA compound in the MCF-7 cell line, while they were calculated to be 17.67 µM for the HB compound in the HUVEC cell line. In addition to the wet laboratory investigations, the ADMET characteristics of the compounds were thoroughly assessed, and none of them were found to violate any drug similarity rules. The synthesized compounds' physicochemical and pharmacological characteristics stayed within Lipinski's RO5 projected limits and have a high bioavailability profile according to ADMET data. In silico toxicity studies revealed that the compounds did not show AMES toxicity and hepatotoxicity. In silico, target receptor predictions of the compounds were performed, and their potential to be kinase inhibitors was high. Therefore, BRAF (V600E) protein kinase was selected target protein in molecular docking studies. Molecular docking studies revealed that all compounds exhibited a significant affinity for crucial residues in the enzyme's active site, confirming the inhibitory nature of BRAF (V600E) protein kinase, showing both polar and apolar interactions.

Comparison of Antifungal Activity of Jaftex Mouthwash and Nystatin Suspension against the Growth of Candida albicans.

Objective: Oral candidiasis is an opportunistic fungal infection in the oral cavity caused by an overgrowth of Candida species, especially Candida albicans. Various herbal agents have been designed to target Candida albicans. The aim of this study was to evaluate the antifungal activity of Jaftex mouthwash and nystatin suspension on the growth of Candida albicans. Materials and methods:In the present in vitro study, a standard strain of Candida albicans was prepared in the form of lyophilized ampoules. Jaftex mouthwash was prepared with an active ingredient (10 g per 100 cc) of aqueous extract of oak fruit hull (Jaft), Zataria multiflora and Satureja bachtiarica. Nystatin oral suspension (100,000 IU/mL) was also prepared. Both mouthwashes were serially diluted using the two-fold serial dilution method (Jaftex: eight-fold dilutions; nystatin suspension: nine-fold dilutions). A volume of 10 ìL of each dilution of Jaftex mouthwash and nystatin suspension was placed on the discs that were linearly inoculated on culture medium and stored in an incubator for 24 hours at 37 °C. The minimum inhibitory concentration (MIC) of the two antifungal agents was determined using the modified E-test. Data were analyzed using SPSS Version 26.0. A p-value less than 0.05 was considered statistically significant. Results:The mean MIC values of Jaftex mouthwash and nystatin suspension were 0.0625 (mg/mL) and 0.0015 (mg/mL), respectively. There was a significant difference between the antifungal effect of Jaftex mouthwash and nystatin suspension on the growth of Candida albicans. Nystatin showed the lowest MIC and greater antifungal activity compared with Jaftex mouthwash. Conclusion:Nystatin increasingly suppressed the growth of Candida albicans. Jaftex mouthwash inhibited the growth of Candida albicans. Since nystatin may show allergic reactions, Jaftex mouthwash can be used as an alternative to nystatin. Due to the synergistic effect of nystatin with thymol, Jaftex mouthwash can be prescribed with nystatin.

Bridging the Chemical Profile and Biomedical Effects of Scutellaria edelbergii Essential Oils.

The present study explored chemical constituents of Scutellaria edelbergii essential oils (SEEO) for the first time, extracted through hydro-distillation, and screened them against the microbes and free radicals scavenging effect, pain-relieving, and anti-inflammatory potential employing standard techniques. The SEEO ingredients were noticed via Gas Chromatography-Mass-Spectrometry (GC-MS) analysis and presented fifty-two bioactive compounds contributed (89.52%) with dominant volatile constituent; 3-oxomanoyl oxide (10.09%), 24-norursa-3,12-diene (8.05%), and methyl 7-abieten-18-oate (7.02%). The MTT assay via 96 well-plate and agar-well diffusion techniques against various microbes was determined for minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), IC50, and zone of inhibitions (ZOIs). The SEEO indicated considerable antimicrobial significance against tested bacterial strains viz. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecalis and the fungal strains Fusarium oxysporum and Candida albicans. The free radicals scavenging potential was noticed to be significant in 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) as compared to 2,2′-azino-bis-3-ethylbenzotiazolin-6-sulfonic acid (ABTS) assays with IC50 = 125.0 ± 0.19 µg/mL and IC50 = 153.0 ± 0.31 µg/mL correspondingly; similarly, the antioxidant standard in the DPPH assay was found efficient as compared to ABTS assay. The SEEO also offered an appreciable analgesic significance and presented 54.71% in comparison with standard aspirin, 64.49% reduction in writhes, and an anti-inflammatory potential of 64.13%, as compared to the standard diclofenac sodium inhibition of 71.72%. The SEEO contain bioactive volatile ingredients with antimicrobial, free radical scavenging, pain, and inflammation relieving potentials. Computational analysis validated the anti-inflammatory potential of selected hit “methyl 7-abieten-18-oate” as a COX-2 enzyme inhibitor. Docking results were very good in terms of docked score (−7.8704 kcal/mol) and binding interactions with the functional residues; furthermore, MD simulation for 100 ns has presented a correlation with docking results with minor fluctuations. In silico, ADMET characteristics supported that methyl 7-abieten-18-oate could be recommended for further investigations in clinical tests and could prove its medicinal status as an anti-inflammatory drug.

Anticandidal and Antibiofilm Effect of Synbiotics including Probiotics and Inulin-Type Fructans.

Background: There is great interest in the search for new alternatives to antimicrobial drugs, and the use of synbiotics is a promising approach to this problem. This study evaluated the growth inhibition and antibiofilm activity of the short-chain fatty acids produced by Lacticaseibacillus rhamnosus and Pediococcus acidilactici in combination with inulin-type fructans against Candida albicans. Methods: The growth inhibition of Candida was evaluated using microdilution analysis in 96-well microtiter plates; different concentrations of cell-free supernatants of Lacticaseibacillus rhamnosus and Pediococcus acidilactici were exposed to Candida albicans. The antibiofilm assessment was carried out using the crystal violet staining assay. The short-chain fatty acids were analyzed by gas chromatography. Results: The clinically isolated Candida albicans interacted with supernatants from Lacticaseibacillus rhamnosus and Pediococcus acidilactici and showed significant growth inhibition and antibiofilm formation versus the controls. Lactate and acetic acid were elevated in the supernatants. The results suggest that the supernatants obtained from the synbiotic combinations of Lacticaseibacillus rhamnosus and Pediococcus acidilactici with inulin-type fructans can inhibit the growth and biofilm formation against a clinically isolated Candida albicans strain. Conclusions: These results suggest that synbiotic formulations could be a promising alternative to antifungal drugs in candidiasis therapy.

Four new N-phenethylbenzamide derivatives from the stems of piper betle and their antimicrobial activity

Four new N-phenethylbenzamide derivatives, named piperbetamides A-D (1–4), and six allylbenzene derivatives (5–10) were isolated from the stems of Piper betle L. Their structures were determined by HR-ESI-MS and NMR spectroscopic methods. Compounds 1–10 were evaluated for their inhibitory effects on the growth of nine microorganisms including five Gram-negative (Escherichia coli, Salmonella enterica serovar Typhimurium, Shigella flexneri, Pseudomonas aeruginosa, and Extended-spectrum beta-lactam resistant Klebsiella pneumoniae), three Gram-positive (Listeria monocytogenes, Methicilin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus faecalis), and one yeast (Candida albicans) strains. Compounds 1, 3, 4, 6 and 10 exhibited potential antimicrobial activity against S. flexneri, L. monocytogenes, methicillin-resistant S. aureus and vancomycin-resistant E. faecalis with minimum inhibitory concentration (MIC) values in the range of 16–32 µg/mL.

Nutritionally rich biochemical profile in essential oil of various Mentha species and their antimicrobial activities.

The Mentha species of family Lamiaceae are famous for their flavor and are commercially used in many food products worldwide. They are widely used to cure digestive problems as well as a natural source of antioxidants and antimicrobials. In this report, the essential oils (EOs) of five Mentha species, namely Mentha citrata, Mentha x piperita, Mentha pulegium, Mentha spicata, and Mentha suaveolens were extracted and their chemical diversity was investigated through gas chromatography-mass spectroscopy (GC-MS). The differential doses (5, 10, and 15µl) of EOs were tested for antimicrobial potential against two gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), five gram-negative bacteria (Escherichia coli, Pseudomonas aeroginosa, Salmonella typhi, Proteus mirabilis and Klebsiella pneumoniae) and a fungal strain (Candida albicans). The GC-MS results revealed the major components in the EOs were Carvone, Linalool, Hotrienol, Menthol, Isopulegone, Furanone, Piperitone, and Thymol. Moreover, the higher dose (15µl) of EOs of M. citrata inhibited the growth of S. typhi and C. albicans (35.8 ± 2.4 and 35.2 ± 2.5mm), M. x piperita inhibited E. coli, B. subtilis, and C. albicans (28.5 ± 3.5, 26.1 ± 2.1, and 25.4 ± 1.1mm), M. pulegium inhibited K. pneumoniae, B. subtilis, and C. albicans (26.8 ± 1.8, 24.2 ± 2.2, and 25.3 ± 0.9mm), M. spicata significantly inhibited S. typhi and B. subtilis (35.7 ± 2.7 and 36.3 ± 2.1mm), and M. suaveolens inhibited K. pneumoniae, C. albicans, and S. typhi (30.8 ± 1.9, 26.9 ± 1.1, and 20.1 ± 0.8mm) respectively. This study concluded that the EOs of M. citrata was effective against S. typhi and C. albicans. The M. x piperita exhibited strong activities against E. coli, B. subtilis, and C. albicans. Furthermore, the M. pulegium strongly inhibited the growth of K. pneumoniae and C. albicans. The EO of M. spicata was more potent against S. typhi and B. subtilis, while the M. suaveolens was comparatively more effective against S. typhi, K. pneumoniae, and C. albicans. These EOs offer a natural source of antimicrobial agents with high commercial values and social acceptance and could be scale up by food and pharmaceutical industries to control pathogenic diseases.

Acquisition of cross-azole tolerance and aneuploidy in Candida albicans strains evolved to posaconazole.

A number of in vitro studies have examined the acquisition of drug resistance to the triazole fluconazole, a first-line treatment for many Candida infections. Much less is known about posaconazole, a newer triazole. We conducted the first in vitro experimental evolution of replicates from 8 diverse strains of Candida albicans in a high level of the fungistatic drug posaconazole. Approximately half of the 132 evolved replicates survived 50 generations of evolution, biased toward some of the strain backgrounds. We found that although increases in drug resistance were rare, increases in drug tolerance (the slow growth of a subpopulation of cells in a level of drug above the resistance level) were common across strains. We also found that adaptation to posaconazole resulted in widespread cross-tolerance to other azole drugs. Widespread aneuploidy was observed in evolved replicates from some strain backgrounds. Trisomy of at least one of chromosomes 3, 6, and R was identified in 11 of 12 whole-genome sequenced evolved SC5314 replicates. These findings document rampant evolved cross-tolerance among triazoles and highlight that increases in drug tolerance can evolve independently of drug resistance in a diversity of C. albicans strain backgrounds.

Digoxin Derivatives Sensitize a Saccharomyces cerevisiae Mutant Strain to Fluconazole by Inhibiting Pdr5p.

The poor outcome of treatments for fungal infections is a consequence of the increasing incidence of resistance to antifungal agents, mainly due to the overexpression of efflux pumps. To surpass this mechanism of resistance, a substance able to inhibit these pumps could be administered in association with antifungals. Saccharomyces cerevisiae possesses an efflux pump (Pdr5p) homologue to those found in pathogenic yeast. Digoxin is a natural product that inhibits Na+, K+-ATPase. The aim of this study was to evaluate whether digoxin and its derivatives (i.e., DGB, digoxin benzylidene) can inhibit Pdr5p, reversing the resistance to fluconazole in yeasts. An S. cerevisiae mutant strain that overexpresses Pdr5p was used in the assays. The effects of the compounds on yeast growth, efflux activity, and Pdr5p ATPase activity were measured. All derivatives enhanced the antifungal activity of fluconazole against S. cerevisiae, in comparison to fluconazole alone, with FICI values ranging from 0.031 to 0.500. DGB 1 and DGB 3 presented combined effects with fluconazole against a Candida albicans strain, with fractional inhibitory concentration index (FICI) values of 0.625 and 0.281, respectively The compounds also inhibited the efflux of rhodamine 6G and Pdr5p ATPase activity, with IC50 values ranging from 0.41 μM to 3.72 μM. The results suggest that digoxin derivatives impair Pdr5p activity. Considering the homology between Pdr5p and efflux pumps from pathogenic fungi, these compounds are potential candidates to be used in association with fluconazole to treat resistant fungal infections.

Discovery of quinolinequinones with N-phenylpiperazine by conversion of hydroxyquinoline as a new class of antimicrobial agents targeting resistant pathogenic microorganisms

The development of new antimicrobial agents is necessary to overcome the emerging antimicrobial resistance among infectious microbial pathogens. Herein, we successfully designed and synthesized quinolinequinones (QQs) with N-phenylpiperazine (QQ1-7) containing strong or weak EDG in the amino moiety by converting hydroxyquinoline (HQ) to the dichloroquinolinequinone (QQ) via chlorooxidation. We performed an extensive antimicrobial activity assessment of the QQs with N-phenylpiperazine (QQ1-7). Among the seven quinolinequinones (QQs) with N-phenylpiperazine tested, QQ3 and QQ4 were the most active molecules against Staphylococcus aureus (ATCC® 29213) with a MIC value of 1.22 μg/mL. In addition to this, while QQ4 was more than six (6) times more effective towards Enterococcus faecalis (ATCC® 29212), QQ3 was twenty-six (26) times more effective against same strain. Furthermore, the evaluation of antimicrobial activity indicated that six of seven synthesized QQs (QQ1-4, QQ6, and QQ7) exhibited superior biological potency, eight (8) times for five of them (QQ1-4 and QQ6) and two (2) times for QQ7, against Staphylococcus epidermidis (ATCC® 12228). Besides, all QQs except QQ5 displayed excellent antifungal activity against the fungi Candida albicans (ATCC® 10231). Among these, the two QQs (QQ3 and QQ4), which showed the lowest values against gram-positive bacterial strains (Staphylococcus aureus (ATCC® 29213), Staphylococcus epidermidis (ATCC® 12228), and Enterococcus faecalis (ATCC® 29212)) as well as fungal strains (Candida albicans (ATCC® 10231) and Candida parapsilosis (ATCC® 22019)), were further evaluated for their biofilm inhibition properties and their mode of action with in vitro potential antimicrobial activity against each of 20 clinically obtained resistant strains of gram-positive bacteria, and bactericidal activity using time-kill curve assay. In this study, we investigated the bactericidal effects of QQ3 against methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans strains. The findings of this study suggest that a significant bactericidal effect was seen with all tested 1 × MIC and 4 × MIC concentrations used within 24 h. Our findings present significant implications for an antimicrobial drug candidate for treating infections, especially those caused by clinically resistant MRSA isolates.

A Series of Novel Bioactive Cyclic Peptides: Synthesis by Head‐to‐Tail Cyclization Approach, Antimicrobial Activity and Molecular Docking Studies

AbstractA new series of cyclic antimicrobial peptides (AMPs) containing D/L‐α‐amino acids have been designed and characterized by spectroscopic techniques. Newly synthesized cyclic peptides were tested for antibacterial and antifungal activities in the hopes of discovering novel clues that may be used to create effective anti‐microbial medicine. Those cyclic AMPs demonstrated good antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus and that was comparable to reference drug Imipenem, as well as good antifungal activity against microbial strains Aspergillus Flavus, Candida Albicans and Candida GlabarataI that was comparable to reference drug Miconazole. In continuous, molecular docking study of the targeted cyclic peptides revealed that they exhibited promising binding interaction networks with DNA gyrase and lanosterol‐14 alpha demethylase, which showed the correlation between biologic activity and docking score of the synthesized analogs.

Selenium-N-heterocyclic carbene (Se-NHC) complexes with higher aromaticity inhibit microbes: synthesis, structure, and biological potential

The synthesis of five selenium complexes bearing imidazole-based N-heterocyclic carbene ligands (Se-NHC) are reported. The adducts were characterized by elemental and spectroscopic analysis (FTIR, 1H and 13C NMR). Single-crystal XRD confirmed the structures of two Se-NHC adducts, VIII and XI. Zone of inhibition (ZOI) values of Se-NHC complexes were evaluated towards two bacterial (Bacillus thuringiensis and Escherichia coli) and one fungal strain (Candida albicans). The most active tested compound was XI with inhibition value of 24.1 ± 0.1 mm against E. coli, and it showed higher activity than Tetracycline (reference drug). Similarly, XI exhibited good inhibition potential against C. albicans (26.5 ± 0.2 mm). The hemolytic assay demonstrated that the tested compounds (VIII-XII) are non-toxic to healthy human blood; however, thrombolysis indicated that VIII-XII could be used as potential thrombolytic agents. It is concluded that Se-NHC carbene adducts having more aromatic rings at terminal nitrogens of imidazole are more effective than other tested compounds. Se-NHC compounds have more efficacy against bacterial strains than fungal strain.

Insight into the Inclusion Complexation of Fluconazole with Sulfonatocalix[4]naphthalene in Aqueous Solution, Solid-State, and Its Antimycotic Activity.

The study aims to assess the interaction between fluconazole and sulfonatocalix[4]naphthalene towards enhancing its dissolution performance and antimycotic activity. A solubility study was carried out at different pH conditions, and the results revealed the formation of a 1:1 molar ratio fluconazole-sulfonatocalix[4]naphthalene inclusion complex with an AL type phase solubility diagrams. The solid powder systems of fluconazole-sulfonatocalix[4]naphthalene were prepared using kneaded and co-evaporation techniques and physical mixtures. DCS, PXRD, TGA-DTG, FT-IR, and in vitro dissolution performance characterize the prepared systems. According to physicochemical characterization, the co-evaporation approach produces an amorphous inclusion complex of the drug inside the cavity of sulfonatocalix[4]naphthalene. The co-evaporate product significantly increased the drug dissolution rate up to 93 ± 1.77% within 10 min, unlike other prepared solid powders. The antimycotic activity showed an increase substantially (p ≤ 0.05, t-test) antimycotic activity of fluconazole co-evaporate mixture with sulfonatocalix[4]naphthalene compared with fluconazole alone against clinical strains of Candida albicans and Candida glabrata. In conclusion, sulfonatocalix[4]naphthalene could be considered an efficient complexing agent for fluconazole to enhance its aqueous solubility, dissolution performance, and antimycotic activity.

Active Antibiotics Production by Actinomycetes Indigenous To Saudi Arabia Soils

Streptomyces are the most popular among the Actinomycetes groups and found in soils worldwide. They form an important part of the soil ecology within the Actinomycetales order. Streptomyces are diverse as secondary antibiotic metabolites such as Novobiocin, Amphotericin, Vancomycin, Neomycin, Gentamicin, Chloramphenicol, Tetracycline, Erythromycin and Nystatin. Thus, the current study was aimed to isolate, identify and assess the active antibiotic metabolites produced by different actinomyces sp. found in Saudi Arabian soils. Six samples were collected from desert soils of the Al Thumamah area and analyzed using GS-MS. Scanning Electron Microscopy was used to identify the bacterial strains along with their antibiotic metabolites effectiveness of secondary metabolites (antibiotics) against different Gram-positive (Bacillus subtilis, Staphylococcus aureus), negative pathogens (Pseudomonas aeruginosa, Escherichia coli, Salmonella suis, and Shigella sonnei) as well as the fungal strain Candida albicans was investigated. Thirty active bacterial (F1-30) strains were isolated from the soil samples and the strains F3, F7, F22, F30 have white, gray, pink, yellow and red colours respectively. Only ten strains (F13, F14, F15, F16, FI7, F18, F19, F20, F21, and F22) were found to have antimicrobial activity against at least one pathogen. The optimum growth environment was pH 4-10, temperature (300C), and NaCl (7% w/v) concentration. According to our findings, the extreme desert environment of Al Thumamah from Saudi Arabia is rich in its actinobacterial population with diverse colouring groups and various physiological and biochemical properties. This shows it’s capability of generating secondary metabolite elements that could inhibit pathogenic microorganisms.

Mechanism of human airway epithelial cell injury induced by Candida albicans infection

Objective: To investigate the immune mechanism of human airway epithelial cell injury induced by invasion of Candida albicans with different biofilm formation abilities. Methods: Twenty-five strains of Candida albicans isolated and cultured in General Hospital of Ningxia Medical University from June to December 2019 were selected, and quality control strain SC5314 was used as the standard strain. An in vitro model of Candida albicans biofilm was established, and the biofilm formation ability of different Candida albicans was detected by crystal violet staining and enzyme plate method. The absorbance value at 570 nm (A570) was determined by enzyme plate method. A570≥0.5, 0.25<A570<0.5 and A570≤0.25 indicated strong biofilm Candida albicans form (SBF), moderate biofilm Candida albicans form (DRF) and weak biofilm Candida albicans form (WBF), respectively. The gas-liquid phase culture model of human airway epithelial cells was isolated and established in vitro and divided into five groups, including blank control group (n=20), standard strain group (n=20), strong biofilm group (n=19), weak biofilm group (n=17) and fluconazole-resistant group (n=18).The morphology of the epithelial cells was observed by scanning electron microscope (SEM), and the expression of marker protein in the model was detected by immunofluorescence in vitro. The level of lactate dehydrogenase (LDH) in cells was detected by microplate method, and the secretion of β-defensin (hBD2), granulocyte macrophage colony stimulating factor(GM-CSF) and granulocyte colony-stimulating factor (G-CSF) was detected by enzyme-linked immunosorbent assay (ELISA). Results: The strong biofilm strains grew with interlacing mycelia, and very few yeast cells could be seen wrapped in them.SEM observed that the mycelia of epithelial cells in gas-liquid phase culture could actively invade epithelial cells, and the expression of acetylated tubulin and keratin in cilia were significantly reduced, while the expression of Ki67 was down-regulated.The LDH levels in the blank control group, standard strain group, strong biofilm group, weak biofilm group, and fluconazole-resistant group were (12.21±5.68), (46.35±6.35), (18.69±4.38), (12.56±3.69), and (13.48±4.28) U/L, respectively, with statistically significant differences (P<0.001). Compared with standard strain group, LDH level in strong biofilm group, weak biofilm group and fluconazole resistant group were significantly decreased (all P<0.01). The hBD2 levels of the five groups were (26.14±0.77), (56.18±0.83), (30.66±2.59), (29.22±0.48), (28.28±1.56) ng/L, respectively, with statistically significant differences(P<0.001). Compared with the blank control group, SC5314-treated epithelial cells induced an increase of intracellular hBD2 expression (P<0.001). The differences in the expression of GM-CSF and G-CSF between different groups were not statistically significant(all P>0.05). Conclusion: Strong biofilm Candida albican can inhibit cell proliferation, disrupt the integrity of epithelial cells and induce cell damage by down-regulating the expression of cell proliferation-related protein.

Variability of pathogenicity factors representative of the human microbiome under the influence of γ-Fe2O3 nanoparticles

Biomedical applications of nanoparticles require deep understanding of their interaction with normal human microflora. Previously, the toxic and mutagenic properties of iron oxide nanoparticles as well as their effect on the growth and morphology of the microflora were extensively investigated. However, the studies related to the variability of microbial pathogenicity factors induced by iron oxide nanoparticles are very limited. Meanwhile, this characteristic of microbes is genetically determined and is important for their survival and distribution in the human body. Therefore, pathogenicity factors are significant indicators of the experimental studies. In this work, the effect of the presence of Fe2O3 nanoparticles obtained by laser target evaporation (LTE) on selected enzymes that demonstrate invasion and aggression factors was evaluated for three reference strains of Candida albicans, Staphylococcus aureus, and Escherichia coli. It was found that the presence of LTE Fe2O3 nanoparticles supplied in the form of water-based suspensions does not induce changes of the above-mentioned parameters.

Silver nanoparticles fabricated by tannic acid for their antimicrobial and anticancerous activity

The present investigation reports a simple and environmentally benign synthesis of nanosized silver involving tannic acid both as a reducing and stabilizing agent. Different analytical tools were used to estimate the exact composition, morphology, and characterization of silver NPs. A sharp surface plasmonic resonance (SPR) band at 410 nm confirms the formation of silver NPs with an optical band gap of 2.36 eV evaluated by UV–visible spectroscopy. Powdered X-ray diffraction analysis shows that the silver NPs were crystallized in a cubic crystal structure and a particle size average of 16.82 nm was computed by transmission electron microscopy. As evidenced by Fourier transformed infrared spectroscopy, tannic acid was an excellent reductant in forming silver NPs from silver ions. Dynamic light scattering noticed the negative charge distribution over the surface of stabilized silver NPs. The present work is mainly devoted to provide significant efforts in developing cancer medicine by fabricating silver NPs. Therefore, the cytotoxic activity against adherent human lung carcinoma cells A549 was evaluated, and the minimal inhibition concentration (MIC or IC50) value was ∼ 300 μM observed (in vitro). It reveals that the silver NPs synthesized by tannic acid were reliable to be an excellent anticancerous agent. Likewise, the antimicrobial activity of silver NPs was also tested by using the disc diffusion method. The gram-negative/positive bacterial strains were used are Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus. However, Candida tropicalis, Candida parapsilosis, and Candida albicans strains were used for antifungal activity. The moderate inhibition activity against bacterial strain was noticed compared to that of fungal strain. This report shows that the tannic acid-mediated silver NPs can be potentially used for removing pathogenic factors and effectively utilized as an anticancerous drug.

Candidemia in cancer patients: phenotypical and molecular-genetic characteristics of antifungal drug resistance, pathogenic factor genes of Candida spp.

Relevance. The global trend of rapid increase in resistance to antifungal drugs due to multiple factors, dictates the need for continuous monitoring of taxonomic structure and susceptibility of nosocomial pathogens, causing invasive fungal infections, for permanent correction of the optimal prevention and treatment strategies. Purpose: to determine antifungal susceptibility of the main yeast pathogens in candidemia in cancer patients, as well as to determine resistance genes and pathogenic factor genes. Material and Methods. Eighty-two strains of Candida spp. isolated from blood of cancer patients from 2015 to 2021 were analyzed. Minimum inhibitory concentrations of fuconazole, voriconazole, posaconazole, anidulafungin and micafungin were determined by a gradient method (E-test, BioMerieux, France). The EUCAST and CLSI criteria were used for MIC value assessment. The genes, associated with pathogenicity factors, and resistance to antifungal drugs were identifed. Results. Our study results based on EUCAST 2020, v.10.0 criteria showed that triazoles, especially fuconazole, were the least effective drugs in empirical therapy for invasive candidiasis (including candidemia). Resistance of Candida spp. fuconazole was superior to that of voriconazole (47.2 % vs 23.2 %, respectively, p&lt;0.01) and posaconazole (47.2 % vs 30.4 %, respectively, p&gt;&lt;0.05). The highest in vitro activity was observed in echinocandins, and anidulafungin was 2 times more active than micafungin (4.1 % of resistant strains vs 11.4 %, respectively), with no statistically signifcant difference (p&gt;0.05). The ERG11 and FKS1 genes associated with resistance to antifungal drugs were detected in 28.6 % of Candida spp. strains. The ERG11 gene was detected in 8.6 % of cases, exclusively in Candida albicans strains. The FKS1 gene was identifed in 20.0 % of strains (85.7 % of them were C. parapsilosis, 7.1 % each were C. tropicalis and C. glabrata). Pathogenic factor genes were identifed in 78.6 % of C. albicans and in 79.1 % of C. parapsilosis strains. Conclusion. Molecular genetic methods for the detection of Candida spp strains carrying resistance genes to antifungal drugs, and the determination of pathogenicity factors are promising trends in searching for biomarkers. They facilitate interpretation of results of microbiological study to assess the ability of Candida spp. strains to develop invasive mycoses.

Phytochemical Screening and In Vitro Antifungal Activity of Selected Medicinal Plants against Candida albicans and Aspergillus niger in West Shewa Zone, Ethiopia.

Antimicrobial resistance to commercially available medications has become a global issue, yet there is still the possibility of developing new drugs from medicinal plants. As a result, the aims of the present study were to screen secondary metabolites and to evaluate in vitro antifungal activities of Brucea antidysenterica, Aloe vera, and Justicia schimperiana. After the plants were identified, their leaves were collected, washed, dried under the shade, pulverized, and extracted with methanol (99.8%) using the maceration technique. The presence of secondary metabolites in plant extracts was screened using various laboratory protocols. The antifungal activities of the plant extract against reference fungal strains of Candida albicans and Aspergillus niger at concentrations of 200, 100, and 50 mg/mL were assessed using the agar-well diffusion method. Ketoconazole (15 μg) was used as a positive control, while 5% dimethyl sulfoxide and/or 5% Tween 80 were used as negative controls. All tests were conducted in triplicate. Alkaloids, flavonoids, and phenols were secondary metabolites found in all plant extracts. The extract of leaves of B. antidysenterica and J. schimperiana formed a mean zone of inhibition of 15.5 ± 0.5 mm and 15.3 ± 0.58 mm, respectively, against Candida albicans at a concentration of 200 mg/mL, whereas extracts of A. vera leaves formed a 12.3 ± 0.58 mm inhibition zone only against Aspergillus niger at 200 mg/mL. In conclusion, the current study found that B. antidysenterica, A. vera, and J. schimperiana had antifungal activity. In addition, all these plants had a variety of secondary metabolites that possibly have antifungal activities. Studies on in vivo investigations and isolation of specific antifungal compounds from these medicinal plants are suggested.