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1.
J Med Microbiol ; 70(4)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33909551

RESUMEN

Candida albicans is an opportunistic pathogen accounting for the majority of cases of Candida infections. Currently, C. albicans are developing resistance towards different classes of antifungal drugs and this has become a global health burden that does not spare Lebanon. This study aims at determining point mutations in genes known to be involved in resistance acquisition and correlating resistance to virulence and ergosterol content in the azole resistant C. albicans isolate CA77 from Lebanon. This pilot study is the first of its kind to be implemented in Lebanon. We carried out whole genome sequencing of the azole resistant C. albicans isolate CA77 and examined 18 genes involved in antifungal resistance. To correlate genotype to phenotype, we evaluated the virulence potential of this isolate by injecting it into BALB/c mice and we quantified membrane ergosterol. Whole genome sequencing revealed that eight out of 18 genes involved in antifungal resistance were mutated in previously reported and novel residues. These genotypic changes were associated with an increase in ergosterol content but no discrepancy in virulence potential was observed between our isolate and the susceptible C. albicans control strain SC5314. This suggests that antifungal resistance and virulence potential in this antifungal resistant isolate are not correlated and that resistance is a result of an increase in membrane ergosterol content and the occurrence of point mutations in genes involved in the ergosterol biosynthesis pathway.


Asunto(s)
Candida albicans/efectos de los fármacos , Candida albicans/genética , Farmacorresistencia Fúngica/genética , Secuenciación Completa del Genoma , Animales , Azoles/farmacología , Candida albicans/química , Candida albicans/patogenicidad , Ergosterol/análisis , Genotipo , Humanos , Líbano , Ratones , Ratones Endogámicos BALB C , Fenotipo , Proyectos Piloto , Mutación Puntual , Virulencia
2.
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
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.
Cell Prolif ; 54(5): e13020, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33694264

RESUMEN

OBJECTIVES: Anti-microbial peptides (AMPs) have been comprehensively investigated as a novel alternative to traditional antibiotics against microorganisms. Meanwhile, Tetrahedral DNA nanostructures (TDNs) have gained attention in the field of biomedicine for their premium biological effects and transportation efficiency as delivery vehicles. Hence, in this study, TDN/Histatin 5 (His-5) was synthesized and the transport efficiency and anti-fungal effect were measured to evaluate the promotion of His-5 modified by TDNs. MATERIALS AND METHODS: Tetrahedral DNA nanostructures/His-5 complex was prepared via electrostatic attraction and characterized by transmission electron microscopy (TEM), polyacrylamide gel electrophoresis (PAGE), dynamic light scattering (DLS) and electrophoretic light scattering (ELS). The anti-fungal effect of the TDN/His-5 complex was evaluated by determining the growth curve and colony-forming units of C. albicans. The morphological transformation of C. albicans was observed by light microscope and scanning electron microscope (SEM). Immunofluorescence was performed, and potassium efflux was detected to mechanistically demonstrate the efficacy of TDN/His-5. RESULTS: The results showed that Histatin 5 modified by TDNs had preferable stability in serum and was effectively transported into C. albicans, leading to the increased formation of intracellular reactive oxygen species, higher potassium efflux and enhanced anti-fungal effect against C. albicans. CONCLUSIONS: Our study showed that TDN/His-5 was synthesized successfully. And by the modification of TDNs, His-5 showed increased transport efficiency and improved anti-fungal effect.


Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , ADN/química , Histatinas/química , Nanoestructuras/química , Antifúngicos/química , Antifúngicos/metabolismo , Estabilidad de Medicamentos , Nanoestructuras/toxicidad , Potasio/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Electricidad Estática
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.
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
7.
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
8.
Int J Nanomedicine ; 16: 119-132, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33447031

RESUMEN

Purpose: This manuscript aimed at encapsulating an antifungal terconazole (TCZ) into innovative novasomes for improving its penetration into the skin and clinically modulating its therapeutic efficacy. Methods: Novasomes containing free fatty acid (FFA) as a penetration enhancer were formulated using ethanol injection technique based on 24 full factorial design to explore the impact of various formulation variables on novasomes characteristics regarding entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formulation was chosen using Design-Expert® software and utilized for further explorations. Results: The chosen formulation (N15; including 100 mg lipid components and Span 80 to oleic acid in a ratio of 2:1 (w/w)) exhibited an EE% = 99.45 ± 0.78%, PS = 623.00 ± 2.97 nm, PDI = 0.40 ± 0.04, and ZP = -73.85 ± 0.64 mV. N15 showed spherical vesicles with a higher deformability index (DI) (9.62 ± 0.15 g) compared to traditional niosomal formulation (0.92 ± 0.12 g). Further, N15 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis-(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition tests revealed a superior TCZ deposition inside the skin from N15 in comparison to traditional niosomal formulation and TCZ suspension. Furthermore, histopathological examination for rats assured the safety of N15 for topical use. A clinical study conducted on infants suffering from napkin candidiasis proved the superiority of N15 to placebo in providing a complete cure of such fungal infections. Conclusion: Concisely, the obtained outcomes confirmed the pronounced efficacy of N15 to successfully treat skin fungal infections.


Asunto(s)
Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Triazoles/administración & dosificación , Administración Tópica , Animales , Antifúngicos/administración & dosificación , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida albicans/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Análisis Factorial , Humanos , Lactante , Liposomas , Masculino , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Ratas , Ratas Wistar , Piel/efectos de los fármacos , Piel/microbiología , Piel/patología , Absorción Cutánea/efectos de los fármacos , Electricidad Estática , Suspensiones , Triazoles/farmacología , Triazoles/uso terapéutico
9.
Int J Biol Macromol ; 173: 99-108, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33460660

RESUMEN

The present investigation reports an in-vitro study using combination of laccase and an enhancer capable of inhibiting the growth of pathogenic microorganisms, preventing biofilm formation, and whitening teeth. Laccase-cinnamic acid system remarkably inhibited the growth of Aggregatibacter actinomycetemcomitans, Candida albicans, S. aureus, and Streptococcus mutans whilst showed no significant effects on Gram-negative bacteria. Data presented that cinnamic acid (10 mM) with laccase (0.125 U ml-1) led to a maximum decrease of about 90%, in S. mutans biofilm formation. The confocal laser scanning microscopy showed considerable detachment of S. mutans cells from glass substratum. The combined laccase-cinnamic acid system could remove teeth discoloration caused by coffee. SEM of the teeth surface exhibited no damages such as surface cracking or fracture. Liquid chromatography-tandem mass spectrometry (LC-MS) and cyclic voltammetry (CV) studies showed that laccase can catalyze the one-electron oxidation of cinnamic acid to the respective radical. This radical can then undergo several fates, including recombination with another radical to form a dimeric species, dismutation of the radical back to cinnamic acid or decarboxylation to give various reduced oxygen species. Therefore, the redox potential values of phenolic monomers/oligomers are related with their biological activities.


Asunto(s)
Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Antibacterianos/farmacología , Cinamatos/farmacología , Proteínas Fúngicas/farmacología , Lacasa/farmacología , Aggregatibacter actinomycetemcomitans/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Ácidos Cafeicos/farmacología , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Catecoles/farmacología , Sinergismo Farmacológico , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Proteínas Fúngicas/aislamiento & purificación , Ácido Gálico/farmacología , Hidroquinonas/farmacología , Lacasa/aislamiento & purificación , Lactobacillus/efectos de los fármacos , Lactobacillus/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Oxidación-Reducción , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Streptococcus mutans/efectos de los fármacos , Streptococcus mutans/crecimiento & desarrollo , Blanqueadores Dentales/farmacología
10.
Int J Biol Macromol ; 170: 664-673, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33387546

RESUMEN

A new class of bio based polymer blends have been prepared from a modified chitosan based benzoxazine precursor (E-ch) and amino cellulose (AC). AC was derived from cellulose with excellent film-forming, biocompatibility and biodegradability property. E-ch was synthesized from eugenol, modified chitosan and paraformaldehyde. The chemical structure was confirmed by FT-IR and 1H NMR analyses. Bio films were prepared by mixing E-ch and AC with diluted acetic acid, in different ratios. These films were further cross-linked by applying heat, via ring-opening polymerization of benzoxazine without any curing agent. FT-IR and DSC were used to study the effects of AC on E-ch to form cross-linked network polymer films [poly(E-ch)/AC]. Hydrogen bonding interactions were found to exist between poly(E-ch) and AC. These kinds of interactions considerably improve the mechanical and thermal properties and char yield of the polymer films. Additionally, these biofilms; poly(E-ch) and poly(E-ch)/AC have been examined for bio-activity with S. aureus. It is confirmed that these bio-films are effective in inhibiting bio-film related infection. In a similar way, both the bio-films act against C. albicans and thus avoid the formation of mycological infection. These results expose that poly(E-ch) and AC bio-films are capable to act as anti-microbial and anti-fungal agents.


Asunto(s)
Antibacterianos/química , Antifúngicos/química , Benzoxazinas/química , Celulosa/química , Polímeros/química , Antibacterianos/farmacología , Antifúngicos/farmacología , Benzoxazinas/farmacología , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Quitosano/química , Eugenol/química , Formaldehído/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Staphylococcus aureus/efectos de los fármacos
11.
Carbohydr Polym ; 255: 117482, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33436242

RESUMEN

A viscous solution of low molecular weight chitosan (CH) at 5% w/v (10.2 kDa, 75 % deacetylated, 1451 cP at 25 °C) was associated with a microemulsion (ME) that undergoes a phase transition after water absorption in situ (≈28 % w/w), forming a more viscous liquid crystal, which was potentially evaluated as a topical vehicle. The ME was selected from a phase diagram, selecting a composition based on Tween® 80 (52 %), myristate isopropyl (28 %), and the aqueous phase (water and polyethylene glycol 400, 60:40 w/w) (20 %), which was after replaced by CH and herbal medicines (HM). HM are alternatives to treat candidiasis, and Stryphnodendron adstringens shell extract, characterized by molecular networking, and Melaleuca alternifolia Chell essential oil (46 % of terpinen-4-ol), showed in vitro activity against Candida albicans. Associating CH in ME improved the mechanical properties of the topical formulation, as adhesiveness, which is an advantageous feature for the topical treatment of vulvovaginal candidiasis.


Asunto(s)
Candida albicans/efectos de los fármacos , Quitosano/química , Fabaceae/química , Melaleuca/química , Aceite de Árbol de Té/química , Candida albicans/crecimiento & desarrollo , Catequina/química , Catequina/aislamiento & purificación , Catequina/farmacología , Emulsiones , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Cristales Líquidos/química , Pruebas de Sensibilidad Microbiana , Peso Molecular , Miristatos/química , Extractos Vegetales/química , Polietilenglicoles/química , Polisorbatos/química , Proantocianidinas/química , Proantocianidinas/aislamiento & purificación , Proantocianidinas/farmacología , Reología , Aceite de Árbol de Té/farmacología , Agua/química
12.
Int J Biol Macromol ; 171: 44-58, 2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33373634

RESUMEN

Fatty acids-assisted superparamagnetic maghemite (γ-Fe2O3) NPs was biologically synthesized using extract of polyherbal drug Liv52 (L52E). The NPs were characterized by UV-vis spectroscopy, FT-IR, SEM, TEM, EDX, XRD and VSM. The major biological molecules present in L52E analysed by GC-MS were saturated fatty acids (palmitic acid 21.95%; stearic acid 13.99%; myristic acid 1.14%), monounsaturated fatty acid (oleic acid 18.43%), polyunsaturated fatty acid (linoleic acid 20.45%), and aromatic phenol (cardanol monoene 11.92%) that could imply in bio-fabrication and stabilization of γ-Fe2O3 NPs. The FT-IR spectra revealed involvement of carboxylic group of fatty acids, amide group of proteins and hydroxyl group of phenolic compounds that acts as reducing and capping agents. The synthesized NPs were used to investigate their antimicrobial, antibiofilm activity against P. aeruginosa, MRSA and C. albicans and anticancer activity on colon cancer cells (HCT-116) for biomedical applications. Further, molecular docking study was performed to explore the interaction of Fe2O3 NPs with major cell wall components i.e., peptidoglycan and mannoproteins. The docking studies revealed that Fe2O3 interacted efficiently with peptidoglycan and mannoproteins and Fe2O3 get accommodated into catalytic cleft of mannoprotein. Due to magnetic property, the biological activity of γ-Fe2O3 can be further enhanced by applying external magnetic field alone or in amalgamation with other therapeutics drugs.


Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Glicoproteínas de Membrana/farmacología , Peptidoglicano/farmacología , Antiinfecciosos/química , Antineoplásicos/química , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Supervivencia Celular/efectos de los fármacos , Células HCT116 , Humanos , Ácido Linoleico/química , Glicoproteínas de Membrana/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Viabilidad Microbiana/efectos de los fármacos , Simulación del Acoplamiento Molecular , Ácido Mirístico/química , Ácido Oléico/química , Ácido Palmítico/química , Peptidoglicano/química , Fenoles/química , Estructura Secundaria de Proteína , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Ácidos Esteáricos/química
14.
Carbohydr Polym ; 251: 117125, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33142657

RESUMEN

Polysaccharide-based nanofibers from Tragacanth Gum (TG) and polyethylene terephthalate (PET) were post-treated with selenium nanoparticles (Se NPs) and also stabilized with TG (SeNPs/TG). DLS, FE-SEM, EDX, TEM, and XRD were employed to verify the synthesis of Se NPs. The relatively narrow size distribution of SeNPs/TG showed through TEM and DLS investigations comparing with Se NPs. The Se NPs formation with and without TG was studied with FTIR confirmed the final stabilized solution due to the bonded hydroxyl groups of TG with Se NPs. Also, a relatively higher antioxidant reported on SeNPs/TG at 0.5-5 mg/mL using DPPH scavenging ability. The Se NPs and SeNPs/TG solutions specified remarkable inhibition against Staphylococcus aureus and Candida albicans; however, no significant antibacterial activities observed on the treated nanofibers. Finally, the uniform migration of fibroblast cells in wound healing of the treated nanofibers with SeNPs/TG proved the value of the products in medical applications.


Asunto(s)
Antiinfecciosos/farmacología , Depuradores de Radicales Libres/farmacología , Nanocompuestos/administración & dosificación , Nanofibras/química , Tereftalatos Polietilenos/química , Selenio/química , Tragacanto/química , Antiinfecciosos/química , Candida albicans/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Depuradores de Radicales Libres/química , Humanos , Nanocompuestos/química , Polisacáridos/química , Staphylococcus aureus/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
15.
Artículo en Inglés | MEDLINE | ID: mdl-32942047

RESUMEN

Independent studies from our group and others have provided evidence that sphingolipids (SLs) influence the antimycotic susceptibility of Candida species. We analyzed the molecular SL signatures of drug-resistant clinical isolates of Candida auris, which have emerged as a global threat over the last decade. This included Indian hospital isolates of C. auris, which were either resistant to fluconazole (FLCR) or amphotericin B (AmBR) or both drugs. Relative to Candida glabrata and Candida albicans strains, these C. auris isolates were susceptible to SL pathway inhibitors such as myriocin and aureobasidin A, suggesting that SL content may influence azole and AmB susceptibilities. Our analysis of SLs confirmed the presence of 140 SL species within nine major SL classes, namely the sphingoid bases, Cer, αOH-Cer, dhCer, PCer, αOH-PCer, αOH-GlcCer, GlcCer, and IPC. Other than for αOH-GlcCer, most of the SLs were found at higher concentrations in FLCR isolates as compared to the AmBR isolates. SLs were at intermediate levels in FLCR + AmBR isolates. The observed diversity of molecular species of SL classes based on fatty acyl composition was further reflected in their distinct specific imprint, suggesting their influence in drug resistance. Together, the presented data improves our understanding of the dynamics of SL structures, their synthesis, and link to the drug resistance in C. auris.


Asunto(s)
Anfotericina B/farmacología , Antifúngicos/farmacología , Candida/metabolismo , Farmacorresistencia Fúngica Múltiple/fisiología , Fluconazol/farmacología , Glucosilceramidas/metabolismo , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Candida albicans/efectos de los fármacos , Candida albicans/aislamiento & purificación , Candida albicans/metabolismo , Candida glabrata/efectos de los fármacos , Candida glabrata/aislamiento & purificación , Candida glabrata/metabolismo , Candidiasis/microbiología , Cromatografía Liquida , Depsipéptidos/farmacología , Farmacorresistencia Fúngica Múltiple/efectos de los fármacos , Ácidos Grasos Monoinsaturados/farmacología , Glucosilceramidas/clasificación , Glucosilceramidas/aislamiento & purificación , Humanos , Lipidómica/métodos , Espectrometría de Masas en Tándem
16.
Carbohydr Polym ; 252: 117192, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33183634

RESUMEN

Microorganisms which adhere to the surfaces of indwelling medical implants develop into a sessile microbial community to form monomicrobial or polymicrobial biofilms. Staphylococcus epidermidis and Candida albicans are the most common pathogens co-isolated from device mediated infections. Hence development of catheters coated with anti-fouling substances is of great interest. In this current study, chitosan, extracted from the shells of marine crab Portunus sanguinolentus was coated over the surface of the urinary catheters and checked for its efficacy to inhibit the adherence of both mono and mixed species biofilms. The Extracted Chitosan (EC) coated catheters showed profound activity in reducing the preformed biofilms and the other virulence factors of the pathogens like slime production in S. epidermidis and yeast to hyphal swtich in C. albicans. Furthermore, qPCR analysis showed that EC could downregulate the virulence genes in both the pathogens when grown as monospecies and mixed species biofilms.


Asunto(s)
Antiinfecciosos/farmacología , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Quitosano/farmacología , Staphylococcus epidermidis/efectos de los fármacos , Catéteres Urinarios/microbiología , Animales , Braquiuros/química
17.
Biomed Pharmacother ; 133: 111043, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33378951

RESUMEN

Nosocomial Candida colonization causes Systemic candidiasis in human with invasive infections in immunocompromised patients. Of all Candida spp., C. albicans is dominant in morbidity of all systemic candidiasis but C. tropicalis is phenomenal in mortality, virulence aspects and resistance development against antifungal drugs. The present study investigated the synergistic anti-virulent activity of myristic acid (MA) and palmitic acid (PA) against insidious dimorphic Candida spp. (C. albicans and C. tropicalis). In vitro and qPCR results revealed the mechanisms of MA-PA combination effectively inhibiting various virulence aspects such as biofilm, hyphal formation, secreted aspartyl proteases, lipases, ergosterol biosynthesis and drug effluxes. Further, in Danio rerio (Zebrafish), the MA-PA treatment increased the survival of animals and also the treated groups showed decreased level of fungal burden compared to the infected controls, after 3rd day of post infection. Histopathology of vital organs and SEM analysis of skin revealed a drastic recovery and reduced the inflammation of both Candida spp. infections in MA-PA treated animals. In addition, MA-PA treatment reduced the haemolysin and increased the susceptibility of Candida spp. in human blood model. Hence, this study suggested the therapeutic utilization of MA-PA as synergistic combination for their anti-inflammatory potency against systemic candidiasis and candidemia.


Asunto(s)
Antiinflamatorios/farmacología , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Candida tropicalis/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Ácido Mirístico/farmacología , Ácido Palmítico/farmacología , Animales , Candida albicans/crecimiento & desarrollo , Candida albicans/patogenicidad , Candida tropicalis/crecimiento & desarrollo , Candida tropicalis/patogenicidad , Candidiasis/microbiología , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Viabilidad Microbiana , Virulencia , Pez Cebra
18.
Biomed Pharmacother ; 133: 111052, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33378958

RESUMEN

The irrational use of medications has increased the incidence of microbial infections, which are a major threat to public health. Moreover, conventional therapeutic strategies are starting to become ineffective to treat these infections. Hence, there is a need to develop and characterize novel antimicrobial compounds. Phytochemicals are emerging as a safe and accessible alternative to conventional therapeutics for treating infectious diseases. Curcumin is extracted from the dried rhizome of the spice turmeric (Curcuma longa (Zingiberaceae)). However, the bioavailability of curcumin is low owing to its lipophilic property and thus has a low therapeutic efficacy in the host. A previous study synthesized structural variants of curcumin, which are called monocurcuminoids (CNs). CNs are synthesized based on the chemical structure of curcumin with only one methyl bridge. The biological activities of four previously synthesized CNs (CN59, CN63, CN67, and CN77), curcumin, and turmeric powder were examined in this study. Gas chromatography-tandem mass spectrometry analysis of curcumin and turmeric powder revealed similar peaks, which indicated the presence of curcumin in turmeric powder. The antioxidant activity of the test compounds was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays. The ABTS radical scavenging activities of the test compounds were similar to those of vitamin C. The minimum inhibitory concentration (MIC) values of the test compounds against seven microbial strains were in the range of 4.06-150 µg/mL. The MIC value was equal to minimum bactericidal concentration value for CN63 (150 µg/mL) and CN67 (120 µg/mL) against Staphylococcus aureus. The treatment combination of CN77 (8.75 or 4.37 µg/mL) and turmeric powder (9.37 or 4.68 µg/mL) exerted synergistic growth-inhibiting effects on Aeromonas hydrophila, Candida albicans, and Pseudomonas aeruginosa. Photodynamic therapy using 2X MIC of CN59 decreased the growth of Enterococcus faecalis by 4.18-fold compared to the control group and completely inhibited the growth of Escherichia coli. The results of the hemolytic assay revealed that the test compounds were not cytotoxic with half-maximal inhibitory concentration values ranging from 49.65-130.9 µM. The anticoagulant activity of most compounds was comparable to that of warfarin but higher than that of heparin. This indicated that these compounds target the intrinsic coagulation pathway. These results demonstrated that these CNs are a safe and promising alternative for curcumin.


Asunto(s)
Antiinfecciosos/farmacología , Antioxidantes/farmacología , Bacterias/efectos de los fármacos , Bioprospección , Candida albicans/efectos de los fármacos , Diarilheptanoides/farmacología , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Animales , Antiinfecciosos/síntesis química , Antiinfecciosos/toxicidad , Antioxidantes/síntesis química , Antioxidantes/toxicidad , Bacterias/crecimiento & desarrollo , Benzotiazoles/química , Compuestos de Bifenilo/química , Coagulación Sanguínea/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Diarilheptanoides/síntesis química , Diarilheptanoides/toxicidad , Farmacorresistencia Microbiana , Hemólisis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/toxicidad , Picratos/química , Oveja Doméstica , Ácidos Sulfónicos/química
19.
J Med Chem ; 64(2): 1116-1126, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33356256

RESUMEN

Due to the evolution and development of antifungal drug resistance, limited efficacy of existing drugs has led to high mortality in patients with serious fungal infections. To develop novel antifungal therapeutic strategies, herein a series of carboline fungal histone deacetylase (HDAC) inhibitors were designed and synthesized, which had potent synergistic effects with fluconazole against resistant Candida albicans infection. In particular, compound D12 showed excellent in vitro and in vivo synergistic antifungal efficacy with fluconazole to treat azole-resistant candidiasis. It cooperated with fluconazole in reducing the virulence of C. albicans by blocking morphological mutual transformation and inhibiting biofilm formation. Mechanism studies revealed that the reversion of drug resistance was due to downregulation of the expression of the azole target gene ERG11 and efflux gene CDR1. Taken together, fungal HDAC inhibitor D12 offered a promising lead compound for combinational treatment of azole-resistant candidiasis.


Asunto(s)
Azoles/uso terapéutico , Candida albicans/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Carbolinas/síntesis química , Carbolinas/uso terapéutico , Farmacorresistencia Fúngica/efectos de los fármacos , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/uso terapéutico , Animales , Biopelículas/efectos de los fármacos , Candida albicans/enzimología , Candidiasis/microbiología , Carbolinas/toxicidad , Quimioterapia Combinada , Femenino , Fluconazol/farmacología , Proteínas Fúngicas/efectos de los fármacos , Hongos/efectos de los fármacos , Hongos/enzimología , Inhibidores de Histona Desacetilasas/toxicidad , Humanos , Hígado/patología , Proteínas de Transporte de Membrana/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Pruebas de Sensibilidad Microbiana
20.
ACS Appl Mater Interfaces ; 13(1): 1524-1534, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33378153

RESUMEN

This study reports a simple and practical method to introduce antimicrobial and biofilm-controlling functions into hydroxyl- or amino-containing polymers such as cellulose using compounds derived from widely used reactive dyes. Two dichloro-s-triazine-based dyes, reactive blue 4 and sodium 4-(4,6-dichloro-1,3,5-triazinylamino)-benzenesulfonate (a colorless reactive "dye"), were covalently attached to cellulose at room temperature by replacing one chloride on the dyes with the hydroxyl groups on cellulose followed by hydrolysis under alkaline conditions to transform the remaining chloride into hydroxyl groups. The chemical reactions were confirmed by FT-IR studies, energy-dispersive X-ray spectroscopy, water contact angle measurement, and zeta potential analysis. The resulting cellulose provided powerful antimicrobial activities against Staphylococcus epidermidis (S. epidermidis, ATCC 35984, Gram-positive bacteria), Escherichia coli (E. coli, ATCC 15597, Gram-negative bacteria), and Candida albicans (C. albicans, ATCC 10231, yeast) and effectively prevented the formation of bacterial or fungal biofilms. The minimum inhibition concentrations of the hydrolyzed dyes were similar to that of phenol. In the zone of inhibition studies using phenolic compounds as positive controls, the hydrolyzed dyes and their model compound cyanuric acid demonstrated antimicrobial functions, suggesting that the antimicrobial activities were associated with the phenol-like hydroxyl groups on the triazine rings. Antimicrobial mechanism investigation indicated that the phenol-like structures on the dyed cellulose caused microbial lysis and leakage of intracellular components. The antimicrobial functions were durable upon repeated washing, and the dyed cellulose showed outstanding biocompatibility toward mammalian cells.


Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Celulosa/análogos & derivados , Celulosa/farmacología , Colorantes/química , Triazinas/química , Antibacterianos/química , Antifúngicos/química , Bencenosulfonatos/química , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candida albicans/fisiología , Fibra de Algodón , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Pruebas de Sensibilidad Microbiana , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/fisiología
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