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3.
Int J Mol Sci ; 22(4)2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33669913

RESUMEN

Candida albicans is a pathogenic fungus that is increasingly developing multidrug resistance (MDR), including resistance to azole drugs such as fluconazole (FLC). This is partially a result of the increased synthesis of membrane efflux transporters Cdr1p, Cdr2p, and Mdr1p. Although all these proteins can export FLC, only Cdr1p is expressed constitutively. In this study, the effect of elevated fructose, as a carbon source, on the MDR was evaluated. It was shown that fructose, elevated in the serum of diabetics, promotes FLC resistance. Using C. albicans strains with green fluorescent protein (GFP) tagged MDR transporters, it was determined that the FLC-resistance phenotype occurs as a result of Mdr1p activation and via the increased induction of higher Cdr1p levels. It was observed that fructose-grown C. albicans cells displayed a high efflux activity of both transporters as opposed to glucose-grown cells, which synthesize Cdr1p but not Mdr1p. Additionally, it was concluded that elevated fructose serum levels induce the de novo production of Mdr1p after 60 min. In combination with glucose, however, fructose induces Mdr1p production as soon as after 30 min. It is proposed that fructose may be one of the biochemical factors responsible for Mdr1p production in C. albicans cells.


Asunto(s)
Candida albicans/efectos de los fármacos , Farmacorresistencia Fúngica/efectos de los fármacos , Fluconazol/farmacología , Fructosa/farmacología , Proteínas Fúngicas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Candida albicans/citología , Carbono/farmacología , Proliferación Celular/efectos de los fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Fructosa/sangre , Proteínas Fluorescentes Verdes/metabolismo , Fracciones Subcelulares/metabolismo
4.
Chemosphere ; 271: 129818, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33736217

RESUMEN

The use of carbohydrates, as a part of surface-active compounds, has been studied due to their biodegradability and nontoxic profile. A series of alkyl glycosides containing d-lyxose and l-rhamnose with alkyl chains of 8-12 carbon atoms were investigated. The effects of structural variations on their physico-chemical and biological properties have been evaluated for a detailed understanding of their properties. Alkyl glycosides were tested on their toxicity against bacterial cells of the genus Pseudomonas (MTT assay), microbiological adhesion to hydrocarbons (MATH assay), cell surface hydrophobicity (Congo red assay), cell membrane permeability (crystal violet assay), and bacterial biofilm formation. Furthermore, their antifungal activity against two pathogenic microorganisms Candida albicans and Aspergillus niger was investigated using the disc diffusion method. Toxicological studies revealed that compounds could reduce the metabolic activity of bacterial cells only moderately but they increased the hydrophobicity of cell surface in Pseudomonas strains. In addition, alkyl glycosides changed the permeability of the cell membranes to the level of 30-40% for this strain. The compounds with an even number of carbon atoms in their alkyl chain promoted stronger bacterial biofilm formation on the glass surface. All studied derivatives demonstrated very strong antifungal activity against fungus A. niger but very small effect against C. albicans. Overall, the results showed that long-chain alkyl glycosides could be considered as inexpensive, biocompatible, nontoxic agents, and serve for the surface design to avoid bacterial adhesion as an alternative solution to antibiotic treatment.


Asunto(s)
Antiinfecciosos , Tensoactivos , Antibacterianos/toxicidad , Antiinfecciosos/toxicidad , Antifúngicos/toxicidad , Candida albicans , Pruebas de Sensibilidad Microbiana , Tensoactivos/toxicidad
5.
Molecules ; 26(5)2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33668096

RESUMEN

Aizoaceae is a large succulent family characterized by many psychoactive species. Aizoon canariense L., a wild neglected plant traditionally used in gastrointestinal ailments, has been the subject of a limited number of phytochemical and biological studies. Therefore, herein, we investigated the in vitro cytotoxic, antimicrobial, and anticholinesteraseactivity of the aerial parts of A. canariense L. and analyzed the phytochemical compositions of the lipoidal and alkaloidal fractions. Petroleum ether extract showed the presence of behenic and tricosylic acid, while an in-depth investigation of the alkaloidal fraction revealed the identification of new adenine based alkaloids (1-5), which were isolated and identified for the first time from Aizoon canariense L. Their structures were elucidated based on extensive spectroscopic analyses. The alkaloidal extract showed a powerful cytotoxic effect (IC50 14-28 µg/mL), with the best effect against colon carcinoma, followed by liver and breast carcinomas. The alkaloidal extract also had a potent effect against Candida albicans and Escherichia coli, with minimum inhibitory concentrations (MIC) values of 312.5 and 625 µg/mL. The in vitro anticholinesterase activity was potent, with IC50 < 200 ng/mL for the tested extracts compared with 27.29 ± 0.49 ng/mL for tacrine.


Asunto(s)
Aizoaceae/química , Alcaloides/farmacología , Antibacterianos/farmacología , Antifúngicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Inhibidores de la Colinesterasa/farmacología , Extractos Vegetales/farmacología , Acetilcolinesterasa/metabolismo , Alcaloides/química , Alcaloides/aislamiento & purificación , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Candida albicans/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Escherichia coli/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Relación Estructura-Actividad
6.
Front Immunol ; 12: 640644, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33717195

RESUMEN

Infection with SARS-CoV-2 can lead to Coronavirus disease-2019 (COVID-19) and result in severe acute respiratory distress syndrome (ARDS). Recent reports indicate an increased rate of fungal coinfections during COVID-19. With incomplete understanding of the pathogenesis and without any causative therapy available, secondary infections may be detrimental to the prognosis. We monitored 11 COVID-19 patients with ARDS for their immune phenotype, plasma cytokines, and clinical parameters on the day of ICU admission and on day 4 and day 7 of their ICU stay. Whole blood stimulation assays with lipopolysaccharide (LPS), heat-killed Listeria monocytogenes (HKLM), Aspergillus fumigatus, and Candida albicans were used to mimic secondary infections, and changes in immune phenotype and cytokine release were assessed. COVID-19 patients displayed an immune phenotype characterized by increased HLA-DR+CD38+ and PD-1+ CD4+ and CD8+ T cells, and elevated CD8+CD244+ lymphocytes, compared to healthy controls. Monocyte activation markers and cytokines IL-6, IL-8, TNF, IL-10, and sIL2Rα were elevated, corresponding to monocyte activation syndrome, while IL-1ß levels were low. LPS, HKLM and Aspergillus fumigatus antigen stimulation provoked an immune response that did not differ between COVID-19 patients and healthy controls, while COVID-19 patients showed an attenuated monocyte CD80 upregulation and abrogated release of IL-6, TNF, IL-1α, and IL-1ß toward Candida albicans. This study adds further detail to the characterization of the immune response in critically ill COVID-19 patients and hints at an increased susceptibility for Candida albicans infection.


Asunto(s)
Aspergillus fumigatus/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Candida albicans/inmunología , Listeria monocytogenes/inmunología , /fisiología , Anciano , Células Cultivadas , Citocinas/metabolismo , Susceptibilidad a Enfermedades , Femenino , Humanos , Tolerancia Inmunológica , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 46(1): 155-161, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645065

RESUMEN

The aim of this paper was to investigate the effect of berberine hydrochloride on the cell wall integrity of Candida albicans hypha. The minimal inhibitory concentration(MIC) of berberine hydrochloride against clinical and standard C. albicans strains was detected by micro liquid-based dilution method; the effect of berberine hydrochloride on the colony formation of C. albicans SC5314 was investigated by spot assay; the effect of berberine hydrochloride on the metabolism of C. albicans SC5314 hypha was checked by XTT reduction assay, and the viability of C. albicans SC5314 hypha was tested by fluorescent staining assay. The effect of berberine hydrochloride on the morphology of C. albicans SC5314 hypha was examined by scanning electron microscope. The changes in the cell wall of C. albicans SC5314 hypha after berberine hydrochloride treatment were detected by transmission electron microscopy. The effect of berberine hydrochloride on ß-glucan from C. albicans SC5314 was detected by flow cytometry. The effect of berberine hydrochloride on hypha-specific gene ECE1 and ß-glucan synthase genes FKS1 and FKS2 in C. albicans was examined by qRT-PCR. The results showed that berberine hydrochloride showed a strong inhibitory effect on both clinical and standard strains of C. albicans, and the MIC was 64-128 µg·mL~(-1). Spot assay, XTT redunction assay and fluorescent staining assay showed that with the increase of berberine hydrochloride concentration, the viability of C. albicans SC5314 gradually decreased. The transmission electron microscopy scanning assay showed that this compound could cause cell wall damage of C. albicans. The flow cytometry analysis showed the exposure degree of C. albicans ß-glucan. The qRT-PCR further showed that berberine hydrochloride could significantly down-regulate hypha-specific gene ECE1 and ß-glucan synthase-related gene FKS1 and FKS2. In conclusion, this compound can down-regulate C. albicans and ß-glucan synthase-related gene expressions, so as to destroy the cell wall structure of C. albicans, expose ß-glucan and damage the integrity of the wall.


Asunto(s)
Berberina , Candida albicans , Antifúngicos/farmacología , Berberina/farmacología , Candida albicans/genética , Pared Celular , Hifa , Pruebas de Sensibilidad Microbiana
8.
Biomed Khim ; 67(1): 42-50, 2021 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-33645521

RESUMEN

Currently, opportunistic fungi of the genus Candida are the main causative agents of mycoses, which are especially severe upon condition of acquired immunodeficiency. The main target for the development of new antimycotics is the cytochrome P450 51 (CYP51) of the pathogenic fungus. Due to the widespread distribution of Candida strains resistancy to inhibitors of the azole class, the screening for CYP51 inhibitors both among non-azole compounds and among clinically used drugs repurposing as antimycotics is becoming urgent. To identify potential inhibitors from the non-azole group, an integrated approach was applied, including bioinformatics analysis, computer molecular modeling, and a surface plasmon resonance (SPR) technology. Using in silico modeling, the binding sites for acetylsalicylic acid, ibuprofen, chlorpromazine and haloperidol (this compounds, according to the literature, showed antimycotic activity) were predicted in the active site of CYP51 of Candida albicans and Candida glabrata. The Kd values of molecular complexes of acetylsalicylic acid, ibuprofen and haloperidol with CYP51, determined by SPR analysis, ranged from 18 µM to 126 µM. It was also shown that structural derivatives of haloperidol, containing various substituents, could be positioned in the active site of CYP51 of Candida albicans with the possible formation of coordination bonds between the hydroxyl groups of the derivatives and the iron atom in the heme of CYP51. Thus, the potential basic structures of non-azole compounds have been proposed, which can be used for the design of new CYP51 inhibitors of Candida fungi.


Asunto(s)
Antifúngicos , Candida , Inhibidores de 14 alfa Desmetilasa/farmacología , Antifúngicos/farmacología , Candida albicans , Sistema Enzimático del Citocromo P-450 , Esterol 14-Desmetilasa
9.
Cell Host Microbe ; 29(3): 311-312, 2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33705697

RESUMEN

Candida albicans is viewed as a harmless commensal in health and a dangerous parasite in disease. Recently in Cell, Doron et al. (2021) reveal that C. albicans in the gut additionally serves as a mutualist by provoking the immune system to generate far-reaching antibodies that defend against invasive fungal infections.


Asunto(s)
Microbioma Gastrointestinal , Agricultura , Proteínas Adaptadoras de Señalización CARD , Candida albicans/inmunología , Humanos , Inmunoglobulina G , Simbiosis
10.
Arch Insect Biochem Physiol ; 106(3): e21771, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33644898

RESUMEN

Antimicrobial proteins (AMPs) are small, cationic proteins that exhibit activity against bacteria, viruses, parasites, fungi as well as boost host-specific innate immune responses. Insects produce these AMPs in the fat body and hemocytes, and release them into the hemolymph upon microbial infection. Hemolymph was collected from the bacterially immunized fifth instar larvae of tasar silkworm, Antheraea mylitta, and an AMP was purified by organic solvent extraction followed by size exclusion and reverse-phase high-pressure liquid chromatography. The purity of AMP was confirmed by thin-layer chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The molecular mass was determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry as 14 kDa, and hence designated as AmAMP14. Peptide mass fingerprinting of trypsin-digested AmAMP14 followed by de novo sequencing of one peptide fragment by tandem mass spectrometry analysis revealed the amino acid sequences as CTSPKQCLPPCK. No homology was found in the database search and indicates it as a novel AMP. The minimum inhibitory concentration of the purified AmAMP14 was determined against Escherichia coli, Staphylococcus aureus, and Candida albicans as 30, 60, and 30 µg/ml, respectively. Electron microscopic examination of the AmAMP14-treated cells revealed membrane damage and release of cytoplasmic contents. All these results suggest the production of a novel 14 kDa AMP in the hemolymph of A. mylitta to provide defense against microbial infection.


Asunto(s)
Péptidos Catiónicos Antimicrobianos , Hemolinfa/metabolismo , Proteínas de Insectos/aislamiento & purificación , Mariposas Nocturnas/metabolismo , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/aislamiento & purificación , Péptidos Catiónicos Antimicrobianos/farmacología , Candida albicans/efectos de los fármacos , Cromatografía en Gel/métodos , Cromatografía Líquida de Alta Presión/métodos , Escherichia coli/efectos de los fármacos , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Proteínas de Insectos/farmacología , Larva/metabolismo , Extracción Líquido-Líquido/métodos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos
11.
J Appl Oral Sci ; 28: e20200639, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33656098

RESUMEN

OBJECTIVE: To evaluate the surface morphology and in vitro leachability of temporary soft linings modified by the incorporation of antifungals in minimum inhibitory concentrations (MIC) for Candida albicans biofilm. METHODOLOGY: Specimens of soft lining materials Softone and Trusoft were made without (control) or with the addition of nystatin (Ny), miconazole (Mc), ketoconazole (Ke), chlorhexidine diacetate (Chx), or itraconazole (It) at their MIC for C. albicans biofilm. The surface analyses were performed using Confocal laser scanning microscopy after 24 h, 7 days, or 14 days of immersion in distilled water at 37ºC. In vitro leachability of Chx or Ny from the modified materials was also measured using Ultraviolet visible spectroscopy for up to 14 days of immersion in distilled water at 37ºC. Data (µg/mL) were submitted to ANOVA 1-factor/Bonferroni (α=0.05). RESULTS: Softone had a more irregular surface than Trusoft. Morphological changes were noted in both materials with increasing immersion time, particularly, in those containing drugs. Groups containing Chx and It presented extremely porous and irregular surfaces. Both materials had biexponential release kinetics. Softone leached a higher concentration of the antifungals than Trusoft (p=0.004), and chlorhexidine was released at a higher concentration than nystatin (p<0.001). CONCLUSIONS: The surface of the soft lining materials changed more significantly with the addition of Chx or It. Softone released a higher concentration of drugs than Trusoft did, guiding the future treatment of denture stomatitis.


Asunto(s)
Alineadores Dentales , Estomatitis Subprotética , Antifúngicos , Candida albicans , Humanos , Cetoconazol , Ensayo de Materiales , Nistatina , Estomatitis Subprotética/tratamiento farmacológico , Propiedades de Superficie
12.
Nat Commun ; 12(1): 1508, 2021 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-33686057

RESUMEN

LC3-associated phagocytosis (LAP) contributes to a wide range of cellular processes and notably to immunity. The stabilization of phagosomes by the macroautophagy machinery in human macrophages can maintain antigen presentation on MHC class II molecules. However, the molecular mechanisms involved in the formation and maturation of the resulting LAPosomes are not completely understood. Here, we show that reactive oxygen species (ROS) produced by NADPH oxidase 2 (NOX2) stabilize LAPosomes by inhibiting LC3 deconjugation from the LAPosome cytosolic surface. NOX2 residing in the LAPosome membrane generates ROS to cause oxidative inactivation of the protease ATG4B, which otherwise releases LC3B from LAPosomes. An oxidation-insensitive ATG4B mutant compromises LAP and thereby impedes sustained MHC class II presentation of exogenous Candida albicans antigens. Redox regulation of ATG4B is thereby an important mechanism for maintaining LC3 decoration of LAPosomes to support antigen processing for MHC class II presentation.


Asunto(s)
Presentación de Antígeno/fisiología , Autofagia/fisiología , Antígenos de Histocompatibilidad Clase II/metabolismo , Fagosomas/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Antígenos Fúngicos , Proteínas Relacionadas con la Autofagia , Candida albicans , Fosfatidilinositol 3-Quinasas Clase III , Cisteína Endopeptidasas/metabolismo , Células HEK293 , Humanos , Macroautofagia , Macrófagos/metabolismo , NADPH Oxidasa 2/metabolismo , Oxidación-Reducción , Fagocitosis/fisiología , Especies Reactivas de Oxígeno/metabolismo
13.
Int J Nanomedicine ; 16: 609-621, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33531804

RESUMEN

Objective: The aim of the current study was to load fenticonazole nitrate, a slightly water-soluble antifungal agent, into terpene-enriched phospholipid vesicles (terpesomes) as a potential delivery system for the management of ocular fungal infection. Methods: Thin film hydration method was used to prepare terpesomes according to a 32 full factorial design to inspect the effect of several variables on vesicles' features. The investigated factors were terpenes type (X1) and terpenes amount (X2) while the dependent responses were encapsulation efficiency percent (Y1), particle size (Y2) and polydispersity index (Y3). Design Expert® program was used to chose the best achieved formula. The selected terpesomes were further optimized via incorporation of a positive charge inducer (stearylamine) to enhance adhesion to the negatively charged mucus covering the eye surface. The in vivo performance of the optimized fenticonazole nitrate-loaded terpesomes relative to drug suspension was evaluated by measuring the antifungal activity (against Candida albicans) retained in the tear's fluid at different time intervals after ocular application in albino rabbits. Results: The optimized terpesomes showed spherical vesicles with entrapment efficiency of 79.02±2.35%, particle size of 287.25±9.55 nm, polydispersity index of 0.46±0.01 and zeta potential of 36.15±1.06 mV. The in vivo study demonstrated significantly higher ocular retention of the optimized fenticonazole nitrate-loaded terpesomes relative to the drug suspension. Moreover, the histopathological studies proved the safety and biocompatibility of the prepared terpesomes. Conclusion: The obtained results verified the potential of the terpesomes for safe and effective ocular delivery of fenticonazole nitrate.


Asunto(s)
Sistemas de Liberación de Medicamentos , Ojo/efectos de los fármacos , Imidazoles/administración & dosificación , Terpenos/farmacología , Administración Cutánea , Animales , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Portadores de Fármacos/química , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Masculino , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Conejos , Suspensiones
14.
Gene ; 780: 145530, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33631248

RESUMEN

Candida spp. have attracted considerable attention as they cause serious human diseases in immunocompromised individuals. The genomes of the pathogenic Candida spp. have been sequenced, but systemic characterizations of their kinomes are yet to be reported. As in various eukaryotes, the protein kinases play crucial regulatory roles in pathogenicity of Candida. Increased frequency of antifungal resistance in Candida spp. requires significant attention to explore novel therapeutic molecules for their control. The present in-silico study involves novel bioinformatics strategies to identify the kinase proteins and their potential drug targets with the purpose to combat fungal infections. The study reports 103, 107 and 106 kinase proteins from 3 Candida spp., C. albicans, C. parapsilosis and C. tropicalis, respectively. Moreover, 79 common kinase proteins were identified, of which 54 proteins play essential roles in Candida spp. and 42 proteins were human non-homologues. Among the essential and human non-homologous protein kinases, 9 were found to be common essential human non-homologues, of which 6 are uniquely present in Candida. These 6 protein kinases namely, Hsl1, Npr1, Ptk2, Kin2, Ksp1 and orf19.3854 (CAALFM_CR06040WA) are involved in various molecular and cellular processes regulating virulence or pathogenicity. Further, these 6 kinases are prioritized as potential drug targets and explored for discovering new lead compounds against candidiasis. The drug repurposing approach for these 6 kinases show 13 approved drugs and investigational compounds that might play substantial inhibitory roles during combating candidiasis.


Asunto(s)
Antifúngicos/farmacología , Candida albicans/enzimología , Candida parapsilosis/enzimología , Candida tropicalis/enzimología , Farmacorresistencia Fúngica/efectos de los fármacos , Proteínas Fúngicas/metabolismo , Proteínas Quinasas/metabolismo , Evaluación Preclínica de Medicamentos , Humanos , Pruebas de Sensibilidad Microbiana
15.
Bull Tokyo Dent Coll ; 62(1): 1-6, 2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33583879

RESUMEN

Candida albicans is the primary candidiasis-causing fungal pathogen in humans, and one of its most important virulence factors is the ability to form biofilms. Moreover, these biofilms are often resistant to antifungal agents, so there is a need to develop alternative elimination strategies and therapeutic agents for such infections. The antifungal activity of resveratrol, a phytoalexin polyphenolic compound, impairs the morphological transition of C. albicans under various hypha-inducing conditions and inhibits growth of the yeast-form and mycelia. The purpose of this study was to investigate the effect of resveratrol against C. albicans biofilm formation. The developmental, sustained, and mature stages of biofilm formation were affected or inhibited by resveratrol. Exposure to resveratrol at the developmental stage inhibited growth of C. albicans in a dose-dependent manner. A >30% reduction was observed in sustained biofilm growth in the presence of 200 µg/ml resveratrol in comparison with in its absence. In terms of disruption of matured biofilm, 6.25-100 µg/ml resveratrol significantly reduced cell viability of C. albicans compared with in a control sample (p<0.05). The present results indicate that resveratrol has the potential to serve as an anti-Candida treatment and preventive tool which functions by inhibiting existing or under-forming C. albicans biofilms.


Asunto(s)
Candida albicans , Candidiasis , Biopelículas , Humanos , Hifa , Resveratrol/farmacología
16.
J Prosthet Dent ; 125(4): 706.e1-706.e6, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33581867

RESUMEN

STATEMENT OF PROBLEM: The high recurrence rates of denture stomatitis may be associated with the resistance of biofilms to therapeutics. Therefore, methods that provide biomaterials with antifungal properties are an attractive solution to improving microbial control. PURPOSE: The purpose of this in vitro study was to modify conventional polymethyl methacrylate (PMMA) through the incorporation of metal methacrylate monomers and to evaluate the physicomechanical and optical properties and antifungal activity of the modified materials. MATERIAL AND METHODS: Experimental denture base acrylic resins were fabricated through the addition of zirconium methacrylate (ZM), tin methacrylate (TM), and di-n-butyldimethacrylate-tin (DNBMT) to the liquid of a commercially available denture base PMMA resin. Unmodified PMMA resin was used as the control. The degree of conversion of the materials was tested through Fourier transform infrared spectroscopy (n=3). A digital spectrophotometer was used to assess the color change of the modified materials (n=8). Differences in Knoop hardness and roughness between experimental groups were also evaluated (n=8). A biofilm accumulation test with Candida albicans (ATCC 62342) (n=4) was performed for 5 days in Sabouraud broth culture supplemented with 10% sucrose. Data were subjected to analysis of variance and the post hoc Tukey honestly significant difference test (α=.05). RESULTS: The degree of conversion and color-change values of the experimental materials were statistically similar to those of the control (P=.593). The incorporation of DNBMT significantly increased the hardness of the modified material (P=.014). The ZM, TM, and DNBMT groups had higher antifungal activity against C. albicans (P=.001) and lower roughness than the control group (control 0.65 ±0.05 µm; ZM 0.34 ±0.09 µm, TM 0.34 ±0.11 µm, and DNBMT 0.41 ±0.08 µm). CONCLUSIONS: The metal-containing methacrylate monomers provided antifungal action to the modified materials without affecting the physicomechanical or optical properties of the denture base resin. ZM, TM, and DNBMT are potential reactive agents for the fabrication of PMMA denture base resins with antifungal properties.


Asunto(s)
Bases para Dentadura , Polimetil Metacrilato , Resinas Acrílicas , Antifúngicos , Candida albicans , Ensayo de Materiales , Metacrilatos , Propiedades de Superficie
17.
Int J Nanomedicine ; 16: 1157-1174, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33623380

RESUMEN

Introduction: Candida albicans is a major opportunistic pathogen that causes a wide range of human infections. Currently available therapeutic agents are limited for treating these fungal infections due to multidrug resistance as well as their nonbiodegradability, poor biocompatibility and toxicity. In order to battle these limitations, we have synthesized a polymeric system as microcarriers to deliver the antifungal drug. The objective of the present study was to immobilize MgO/CuO nanocomposite and nystatin-loaded MgO/CuO nanocomposites in nontoxic, nonimmunogenic, biodegradable and biocompatible sodium alginate microspheres for the first time. Materials and Methods: Nanoparticle-loaded sodium alginate microspheres were prepared by ionotropic gelation technique using calcium chloride as a cross-linker. Synthesized microspheres were characterized using standard characterization techniques and were evaluated for biological activity against MDR strain of C. albicans. Results: Characterization of microspheres by Fourier-transform infrared spectroscopy confirmed loading of Nys-MgO/CuO NPs, scanning electron microscopy (SEM) revealed rough spherical beads with a highly porous surface having an average size in the range of 8-10 µm. X-ray diffraction (XRD) analyzed its semicrystalline structure. Entrapment efficiency of Nys-MgO/CuO NPs was 80% and release kinetic study revealed sustained and prolonged release of drug in pH 5.5. Flow cytometry analysis showed yeast cell death caused by Nys-MgO/CuO MS exhibits late apoptotic features. In cytotoxicity assay 5-14 mg of microspheres did not cause hemolysis. Microspheres reduced virulence traits of C. albicans such as germ tube and biofilm formation were compromised at concentration of 5 mg/mL. Antimicrobial assessment results revealed a pronounced inhibitory effect against C. albicans. Conclusion: The in vitro experiments have shown promising results based on good stability, Nys-MgO/CuO NP-encapsulated microspheres can be used as a prolonged controlled release system against MDR pathogenic C. albicans.


Asunto(s)
Alginatos/química , Candida albicans/patogenicidad , Cobre/química , Resistencia a Múltiples Medicamentos , Óxido de Magnesio/química , Microesferas , Nanocompuestos/química , Nistatina/farmacología , Antiinfecciosos/farmacología , Biopelículas/efectos de los fármacos , Liberación de Fármacos , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Cinética , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Fenotipo , Espectroscopía Infrarroja por Transformada de Fourier , Virulencia/efectos de los fármacos , Factores de Virulencia/metabolismo , Difracción de Rayos X
18.
ACS Appl Mater Interfaces ; 13(6): 7070-7079, 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33544596

RESUMEN

The anion-exchange capacity of the cell-wall sulfated polysaccharide of the red microalga Porphyridium sp. can be exploited for the complexation of metal ions (e.g., Cu, Zn, Ag) to produce novel materials with new bioactivities. In this study, we investigated this algal polysaccharide as a platform for the incorporation of copper as Cu2O. Chemical and rheological characterization of the Cu2O-polysaccharide complex showed that the copper is covalently bound to the polysaccharide and that the complex exhibits higher viscosity and conductivity than the native polysaccharide. Examination of the complex's inhibitory activity against the bacteria Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Bacillus subtilis and the fungus Candida albicans revealed a relatively high antimicrobial activity, especially against C. albicans (92% growth inhibition) as compared to the polysaccharide and to Cu2O alone. The antibiofilm activity was also found against P. aeruginosa PA14 and C. albicans biofilms. An atomic force microscopy examination of the surface morphology of the complex revealed needle-like structures (spikes), approximately 10 nm thick, protruding from the complex surface to a maximum height of 1000 nm, at a density of about 5000/µm2, which were not detected in the native polysaccharide. It seems that the spikes on the surface of the Cu2O-polysaccharide complex are responsible for the antimicrobial activities of the complex, that is, for disruption of microbial membrane permeability, leading to cell death. The study thus indicates that the superior qualities of the novel material formed by complexion of Cu2O to the polysaccharide should be studied further for various biotechnological applications.


Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Cobre/farmacología , Microalgas/química , Polisacáridos/farmacología , Sulfatos/farmacología , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Bacillus subtilis/efectos de los fármacos , Candida albicans/efectos de los fármacos , Cobre/química , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Polisacáridos/química , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Sulfatos/química , Propiedades de Superficie
19.
Int J Nanomedicine ; 16: 941-950, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603361

RESUMEN

Purpose: Candidemia infection is common in the clinic and has a high mortality rate. Candida albicans, Candida tropicalis, and Candida krusei are very important and common pathogenic species. Candida is difficult to isolate from clinical samples and culture, and immunological detection cannot distinguish these related strains. Furthermore, Candida has a complex cell wall, which causes difficulties in the extraction of DNA for nucleic acid detection. The purpose of this study was to establish a protocol for the direct identification of Candida from serum. Materials and Methods: We synthesized Fe3O4@PEI (where PEI stands for polyethylenimine) magnetic nanoparticles to capture Candida and prepared positively charged silver nanoparticles (AgNPs+) as the substrate for surface-enhanced Raman scattering (SERS). Candida was directly identified from serum by SERS detection. Results: Orthogonal partial least squares discriminant analysis (OPLS-DA) was used as the multivariate analysis tool. Principal component analysis confirmed that this method can clearly distinguish common Candida. After 10-fold cross-validation, the accuracy of training data in this model was 100% and the accuracy of test data was 99.8%, indicating that the model has good classification ability. Conclusion: The detection could be completed within 40 minutes using Fe3O4@PEI and AgNPs+ prepared in advance. This is the first time that Fe3O4@PEI was used in the detection of Candida by SERS. We report the first rapid method to identify fungi directly from serum without breaking the cell wall to extract DNA from the fungi.


Asunto(s)
Candida/aislamiento & purificación , Nanopartículas de Magnetita/química , Nanopartículas del Metal/química , Plata/química , Espectrometría Raman/métodos , Candida albicans , Análisis Discriminante , Humanos , Análisis de los Mínimos Cuadrados , Nanopartículas de Magnetita/ultraestructura , Nanopartículas del Metal/ultraestructura , Análisis Multivariante , Polietileneimina/química
20.
Allergol. immunopatol ; 49(1): 118-127, ene.-feb. 2021. ilus, tab, graf
Artículo en Inglés | IBECS | ID: ibc-199236

RESUMEN

Chronic mucocutaneous candidiasis (CMC) is characterized by a chronic or recurrent non-invasive infection, mainly due to Candida albicans, in skin, nails, and mucous membranes, associated in some cases with autoimmune manifestations. The key immune defect is a disruption of the action of cytokine IL-17, whose most common genetic etiology is STAT1 gene gain-of-function (GOF) mutations. The initial appropriate treatment for fungal infections is with azoles. However, the frequent occurrence of drug resistance is the main limitation. Therefore, identification of the underlying inborn error if immunity in CMC may allow to widen therapeutic options aimed at restoring immunological function. Type I and II Janus kinase-inhibitors have been shown to control CMC in cases associated with STAT1 GOF. In this review, we delve into the pathogenesis of CMC and the underlying immune mechanisms. We describe the reported genetic defects in which CMC is the main manifestation. Diagnostic and therapeutic approaches for these patients are also offered


No disponible


Asunto(s)
Humanos , Candidiasis Mucocutánea Crónica/etiología , Candidiasis Mucocutánea Crónica/diagnóstico , Piel/inmunología , Candidiasis Mucocutánea Crónica/fisiopatología , Resistencia a Medicamentos/inmunología , Candida albicans/inmunología , Candida albicans/aislamiento & purificación
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