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1.
Curr Microbiol ; 79(2): 58, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982237

RESUMO

The study aimed to evaluate the safety of copper ion sterilization based on copper ion residues in zebrafish (Brachydanio rerio), as well as bacterial community structure and diversity in recirculating aquaculture systems (RASs). The copper ion content was determined using national food safety standard GB 5009.13-2017. Bacterial community structures and alpha and beta diversity indexes were examined using the 16S rRNA gene sequences produced by Illumina HiSeq sequencing. The results revealed no significant copper ion enrichment in B. rerio when the copper ion concentration was 0.15 mg/L. The relative abundances of Erythrobacter, nitrite bacteria, and Flavanobacteria were clearly higher in the treatment group than in the control and differences in bacterial species richness and diversity were obvious. In addition, there was no sharp decrease in the microflora at the outflow of the copper ion generator. In conjunction with the changes in ammonia nitrogen, nitrate, and nitrite concentrations during the experiment, the results indicated that there were no significant effects on the purification efficacy of the biological filter, but the abundances of beneficial bacteria increased significantly. This is of great relevance in order to understand the response of bacterial communities affected by changing environmental conditions, such as copper ion sterilization.


Assuntos
Cobre , Peixe-Zebra , Animais , Aquicultura , Bactérias/genética , Cobre/farmacologia , Água Doce , RNA Ribossômico 16S/genética , Esterilização
2.
J Colloid Interface Sci ; 608(Pt 1): 749-757, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34634547

RESUMO

Cuprous oxide (Cu2O) and cupric oxide (CuO) are widely available and low cost raw materials. Their applications as precursors for wet chemical synthesis of metallic Cu materials are greatly limited due to their insoluble in water and most organic solvents. In this work, copper superfine particles (Cu SPs) are synthesized using Cu2O and CuO as precursors via a heating process in monoethanoamine (MEA). Due to the strong coordinating character, Cu2O and CuO can be partially dissolved in MEA. The dissolved copper source is reduced by MEA at elevated temperature with the drastically releasing of NH3. As the dissolved copper source is reduced, more oxide will be dissolved and finally leads to the full reduction of Cu2O and CuO to produce the Cu SPs. The advantage of this synthesis method is that MEA acts as both the solvent and the reducing agent. The antimicrobial properties are investigated to find that the obtained Cu SPs depress the growth of Escherichia coli (E. coli) and Staphylococcus aureus (St. aureus) efficiently. More interesting, the composites produced via curing Cu2O and CuO with a small amount of MEA also exhibit excellent antimicrobial activity, indicating the MEA curing method is high-efficiency. The synthesis is low cost, high-efficiency, high atom-economy and up-scale synthesizing easily, which will benefit the wide applications of Cu SPs.


Assuntos
Anti-Infecciosos , Cobre , Anti-Infecciosos/farmacologia , Cobre/farmacologia , Escherichia coli , Etanolamina , Óxidos
3.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112194, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34749193

RESUMO

Mg, Zn and Ce-doped CuO/HA composites were prepared by a two-step sol-gel and hydrothermal process. SEM images showed a spherical appearance of HA and a needle-like morphology for doped CuO. XRD patterns revealed that all doped CuO/HA composites exhibited a hexagonal crystal structure of HA and a monoclinic crystal structure of CuO with no impurities. ICP analysis indicated that with the increase of loading amount of doped CuO, the concentrations of Cu2+ ions and doping ions released from composites increased. Moreover, CuO/HA composites exhibit improved antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as compared with HA. When the loading amount of doped CuO in composites increased to 15 wt%, the composites exhibited the best antibacterial activity and complete bacterial growth inhibition effect. Furthermore, the CCK-8 assay revealed that the doped CuO/HA composites are noncytotoxic and can promote the proliferation of osteosarcoma cells. This work highlights the potential of the doped CuO/HA composites with significant antibacterial activity, bioactivity and cell compatibility for potential biomedical applications in dental implants and bone regeneration.


Assuntos
Cobre , Durapatita , Antibacterianos/farmacologia , Cobre/farmacologia , Escherichia coli , Óxidos , Staphylococcus aureus
4.
J Colloid Interface Sci ; 608(Pt 1): 30-39, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624763

RESUMO

The present work reports a novel antibacterial nanocomposite film comprising of copper nanowire impregnated biocompatible hypromellose using polyethylene glycol as a plasticiser. Detailed physico-chemical characterization using X-ray diffraction, Fourier transform infrared spectroscopy, UV-Visible spectroscopy and electron microscopy shows uniform dispersion of copper nanowire in the polymer matrix without any apparent oxidation. The film is flexible and shows excellent antibacterial activity against both Gram positive and negative bacteria at 4.8 wt% nanowire loading with MIC values of 400 µg/mL and 500 µg/mL for E. coli and S. aureus respectively. Investigation into the antibacterial mechanism of the nanocomposite indicates multiple pathways including cellular membrane damage caused by released copper ions and reactive oxygen species generation in the microbial cell. Interestingly, the film showed good biocompatibility towards normal human dermal fibroblast at minimum bactericidal concentration (MBC). Compared to the copper nanoparticles reported earlier in vitro studies, this low cytotoxicity of copper nanowires is due to the slow dissolution rate of the film and production of lower amount of ROS producing Cu2+ ions. Thus, the study indicates a strong potential for copper nanowire-based composites films in broader biomedical and clinical applications.


Assuntos
Nanopartículas Metálicas , Nanocompostos , Nanofios , Antibacterianos/farmacologia , Cobre/farmacologia , Escherichia coli , Humanos , Derivados da Hipromelose , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus , Difração de Raios X
5.
Bioorg Chem ; 118: 105474, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34794102

RESUMO

The worldwide prevalence of NDM-1-producing Gram-negative pathogens has drastically undermined the clinical efficacy of carbapenems, prompting a need to devise an effective strategy to preserve their clinical value. Here we constructed a focused compound library of dithiocarbamates and systematically evaluated their potential synergistic antibacterial activities combined with copper. SA09-Cu exhibited excellent inhibition against a series of clinical NDM-1-producing carbapenem-resistant Enterobacteriaceae (CRE) in restoring meropenem effect, and slowed down the development of carbapenem resistance. Enzymatic kinetic and isothermal titration calorimetry studies demonstrated that SA09-Cu was a noncompetitive NDM-1 inhibitor. The electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) revealed a novel inhibition mechanism, which is that SA09-Cu could convert NDM-1 into an inactive state by oxidizing the Zn(II)-thiolate site of the enzyme. Importantly, SA09-Cu showed a unique redox tuning ability, and avoided to be reduced by intracellular thiols of bacteria. In vivo experiments indicated that SA09 combined with CuGlu could effectively potentiate MER's effect against NDM-1-producing E. coli (EC23) in the murine infection model. This study provides a highly promising scaffold in developing novel inhibitors to combat NDM-1-producing CREs.


Assuntos
Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Inibidores Enzimáticos/farmacologia , Tiocarbamatos/farmacologia , beta-Lactamases/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tiocarbamatos/química
6.
J Colloid Interface Sci ; 607(Pt 2): 1825-1835, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34688975

RESUMO

Metal chalcogenides have been intensively investigated as antibacterial agents due to their unique structures and superior photoactivities. Herein, various structures of copper sulfide (CuS), a metal chalcogenide, such as microspheres (MSs), nanosheets (NSs), and nanoparticles (NPs), were developed in this work for antibacterial applications. A hydrothermal process was utilized to synthesize CuS MSs, CuS NSs, and CuS NPs. Under simulated solar light and near-infrared (NIR) light irradiation, the antibacterial behaviors, reactive oxygen species (ROS) production, and light-driven antibacterial mechanisms of CuS MSs, CuS NSs, and CuS NPs were demonstrated with the bacterium Escherichia coli (E. coli). Bacterial growth curves and ROS generation tests indicated that CuS NSs and CuS NPs had higher light-driven antibacterial activities than that of CuS MSs. ROS of hydroxyl (·OH) and superoxide anion radicals (O2-) were investigated via an electron spin resonance (ESR) spectroscopic analysis by respectively incubating CuS MSs, CuS NSs, and CuS NPs with E. coli under simulated solar light irradiation. Furthermore, E. coli incubated with CuS NPs and CuS NSs showed substantial bacterial degradation after NIR laser irradiation, which was attributed to their photothermal killing effects. Light-driven antibacterial mechanisms of CuS NSs and CuS NPs were investigated, and we discovered that under simulated solar and NIR light irradiation, CuS NSs and CuS NPs produced photoinduced electrons, and the copper ions and photoinduced electrons then reacted with atmospheric moisture to produce hydroxide and superoxide anion radicals and heat, resulting in bacterial mortality.


Assuntos
Cobre , Nanopartículas , Antibacterianos/farmacologia , Cobre/farmacologia , Escherichia coli , Sulfetos
7.
Int J Mol Sci ; 22(24)2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34948419

RESUMO

Polyurethane foams (PUFs) have attracted attention as biomaterials because of their low adhesion to the wound area and suitability as biodegradable or bioactive materials. The composition of the building blocks for PUFs can be controlled with additives, which provide excellent anti-drug resistance and biocompatibility. Herein, nanosized Cu-BTC (copper(II)-benzene-1,3,5-tricarboxylate) was incorporated into a PUF via the crosslinking reaction of castor oil and chitosan with toluene-2,4-diisocyanate, to enhance therapeutic efficiency through the modification of the surface of PUF. The physical and thermal properties of the nanosized Cu-BTC-incorporated PUF (PUF@Cu-BTC), e.g., swelling ratio, phase transition, thermal gravity loss, and cell morphology, were compared with those of the control PUF. The bactericidal activities of PUF@Cu-BTC and control PUF were evaluated against Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus. PUF@Cu-BTC exhibited selective and significant antibacterial activity toward the tested bacteria and lower cytotoxicity for mouse embryonic fibroblasts compared with the control PUF at a dose of 2 mg mL-1. The Cu(II) ions release test showed that PUF@Cu-BTC was stable in phosphate buffered saline (PBS) for 24 h. The selective bactericidal activity and low cytotoxicity of PUF@Cu-BTC ensure it is a candidate for therapeutic applications for the drug delivery, treatment of skin disease, and wound healing.


Assuntos
Antibacterianos/administração & dosagem , Materiais Biocompatíveis/química , Cobre/administração & dosagem , Estruturas Metalorgânicas/administração & dosagem , Poliuretanos/química , Antibacterianos/química , Antibacterianos/farmacologia , Cobre/química , Cobre/farmacologia , Portadores de Fármacos/química , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/prevenção & controle , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos
8.
Int J Mol Sci ; 22(24)2021 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-34948146

RESUMO

Copper (Cu) is an essential element involved in various metabolic processes in plants, but at concentrations above the threshold level, it becomes a potential stress factor. The effects of two different cytokinins, kinetin (KIN) and 6-benzylaminopurine (BAP), on chlorophyll a fluorescence parameters, stomatal responses and antioxidation mechanisms in castor (Ricinus communis L.) under Cu2+ toxicity was investigated. Ricinus communis plants were exposed to 80 and 160 µM CuSO4 added to the growth medium. Foliar spraying of 15 µM KIN and BAP was carried out on these seedlings. The application of these cytokinins enhanced the tissue water status, chlorophyll contents, stomatal opening and photosynthetic efficiency in the castor plants subjected to Cu2+ stress. The fluorescence parameters, such as Fm, Fv/Fo, Sm, photochemical and non-photochemical quantum yields, energy absorbed, energy trapped and electron transport per cross-sections, were more efficiently modulated by BAP application than KIN under Cu2+ toxicity. There was also effective alleviation of reactive oxygen species by enzymatic and non-enzymatic antioxidation systems, reducing the membrane lipid peroxidation, which brought about a relative enhancement in the membrane stability index. Of the various treatments, 80 µM CuSO4 + BAP recorded the highest increase in photosynthetic efficiency compared to other cytokinin treatments. Therefore, it can be concluded that BAP could effectively alleviate the detrimental effects of Cu2+toxicity in cotyledonary leaves of R. communis by effectively modulating stomatal responses and antioxidation mechanisms, thereby enhancing the photosynthetic apparatus' functioning.


Assuntos
Compostos de Benzil/farmacologia , Cobre/farmacologia , Fotossíntese/efeitos dos fármacos , Purinas/farmacologia , Ricinus/metabolismo , Plântula/metabolismo
9.
Int J Nanomedicine ; 16: 7727-7739, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824531

RESUMO

Introduction: Dental caries is a biofilm-dependent disease that largely relies on the ability of Streptococcus mutans to synthesize exopolysaccharide matrix. Graphene oxide-based metal nanomaterials, as the derivatives of graphene, are potent agents against pathogens by their impressive antibacterial and anti-biofilm biofunctions. Previously, we fabricated the novel graphene oxide-copper nanocomposites (GO-Cu), maintaining a long-term release of copper nanoparticles. Here, the biofunctionalization of GO-Cu nanocomposites against cariogenic S. mutans is investigated. Methods: Growth curve observation and colony forming units counting were applied to detect the antibacterial effect of GO-Cu nanocomposites on S. mutans. Scanning electron microscopy and the crystal violet assay were used to detect nanocomposite effects on biofilm forming ability. The production and distribution of exopolysaccharides within biofilm was analyzed and the expression of genes required for biofilm formation was explored. Moreover, the regulatory landscape of GO-Cu nanocomposites on S. mutans pathogenicity was probed. Results: It has been found that GO-Gu nanocomposites were antibacterial to S. mutans and 10 µg/mL GO-Cu nanocomposites could inhibit the bacteria bioactivity instead of killing them. The biomass of S. mutans biofilm was significantly reduced when treated with 10 µg/mL GO-Cu nanocomposites. Also, 10 µg/mL GO-Cu nanocomposites could alter the biofilm architecture and impair exopolysaccharides production and distribution, and dysregulated the expression of exopolysaccharide-associated genes. Conclusion: In all, we found low-dose GO-Cu nanocomposites could disrupt exopolysaccharide matrix assembly and further impair optimal biofilm development with minimal cytotoxicity. Therefore, GO-Cu nanocomposites can open up a new avenue for the development of alternative anti-caries biomaterials.


Assuntos
Cárie Dentária , Grafite , Nanocompostos , Antibacterianos/farmacologia , Biofilmes , Cariostáticos , Cobre/farmacologia , Humanos , Streptococcus mutans
10.
Molecules ; 26(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34771072

RESUMO

The synthesis of nanoparticles is most important in the context of cancer therapy, particularly copper nanoparticles, which are widely used. In this work, copper(II)-tyrosinase was isolated from potato peel powder. Copper nanoparticles (Tyr-Cu(II)-AEEA NPs) were synthesized via the reaction of tyrosinase with N-aminoethylethanolamine to produce Cu(II)-NPs and these were characterized by means of FT-IR, UV-Spectroscopy, XRD, SEM, TEM and a particle size analyzer. These Tyr-Cu(II)-AEEA NPs were tested as anticancer agents against MCF-7 breast cancer cells. Fluorescence microscopy and DNA fragmentation were also performed, which revealed the inhibiting potentials of Cu(II)-AEEA NPs and consequent cell death; Tyr-Cu(II)-AEEA NPs show potential cytotoxicity activity and this nano material could be contemplated as an anticancer medicament in future investigations.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Etanolaminas/farmacologia , Nanopartículas Metálicas/química , Monofenol Mono-Oxigenase/metabolismo , Solanum tuberosum/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cobre/química , Cobre/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Etanolaminas/química , Etanolaminas/metabolismo , Feminino , Humanos , Células MCF-7 , Microscopia de Fluorescência , Solanum tuberosum/química
11.
Molecules ; 26(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34500790

RESUMO

The aim of this study was to determine the pattern of alleviation effects of calcium (Ca), magnesium (Mg), and potassium (K) on copper (Cu)-induced oxidative toxicity in grapevine roots. Root growth, Cu and cation accumulation, reactive oxygen species (ROS) production, and antioxidant activities were examined in grapevine roots grown in nutrient solutions. The experimental setting was divided into three sets; each set contained a check (Hoagland solution only) and four treatments of simultaneous exposure to 15 µM Cu with four cation levels (i.e., Ca set: 0.5, 2.5, 5, and 10 mM Ca; Mg set: 0.2, 2, 4, and 8 mM Mg; K set: 0.6, 2.4, 4.8, and 9.6 mM K). A damage assessment model (DAM)-based approach was then developed to construct the dose-effect relationship between cation levels and the alleviation effects on Cu-induced oxidative stress. Model parameterization was performed by fitting the model to the experimental data using a nonlinear regression estimation. All data were analyzed by a one-way analysis of variance (ANOVA), followed by multiple comparisons using the least significant difference (LSD) test. The results showed that significant inhibitory effects on the elongation of roots occurred in grapevine roots treated with 15 µM Cu. The addition of Ca and Mg significantly mitigated phytotoxicity in root growth, whereas no significant effect of K treatment on root growth was found. With respect to oxidative stress, ROS and malondialdehyde (MDA) contents, as well as antioxidant (superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)) activities, were stimulated in the roots after exposure to 15 µM Cu for three days. Moreover, H2O2 levels decreased significantly as Ca, Mg, and K concentrations increased, indicating that the coexistence of these cations effectively alleviated Cu-induced oxidative stress; however, alleviative effects were not observed in the assessment of the MDA content and antioxidant enzyme activities. Based on the DAM, an exponential decay equation was developed and successfully applied to characterize the alleviative effects of Ca, Mg, and K on the H2O2 content induced by Cu in the roots. In addition, compared with Mg and K, Ca was the most effective cation in the alleviation of Cu-induced ROS. Based on the results, it could be concluded that Cu inhibited root growth and Ca and Mg absorption in grapevines, and stimulated the production of ROS, lipid peroxidation, and antioxidant enzymes. Furthermore, the alleviation effects of cations on Cu-induced ROS were well described by the DAM-based approach developed in the present study.


Assuntos
Cálcio/farmacologia , Cobre/farmacologia , Magnésio/farmacologia , Raízes de Plantas/efeitos dos fármacos , Potássio/farmacologia , Vitis/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Vitis/crescimento & desenvolvimento
12.
Bioresour Technol ; 341: 125859, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34523571

RESUMO

This study aimed to investigate the short-term response of abundant-rare genera and antibiotic resistance genes (ARGs) to azithromycin (AZM, 0.05-40 mg/L) and copper (1 mg/L) combined pollution in activated sludge nitrification system at low temperature. Nitrification was as expected inhibited in stress- and post-effects periods under AZM concentration higher than 5 mg/L. Abundant and rare taxa presented dissimilar responses based on full-scale classification. Conditionally rare or abundant taxa (CRAT) were keystone taxa. Relative abundance of ammonia-oxidizing archaea increased, and three aerobic denitrifying bacteria (Brevundimonas, Comamonas and Trichococcus) were enriched (from 9.83% to 68.91% in total). Ammonia nitrogen assimilating into Org-N and denitrification may be nitrogen pathways based on predict analysis. 29 ARGs were found with more co-occurrence patterns and high concentration of AZM (greater than 5 mg/L) caused their proliferation. Importantly, expect for some abundant taxa, rare taxa, potential pathogens and nitrogen-removal functional genera were the main potential hosts of ARGs.


Assuntos
Microbiota , Nitrificação , Antibacterianos/farmacologia , Azitromicina/farmacologia , Cobre/farmacologia , Desnitrificação , Resistência Microbiana a Medicamentos/genética , Laboratórios , Nitrogênio/análise , Esgotos , Temperatura
13.
Mater Sci Eng C Mater Biol Appl ; 128: 112297, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474848

RESUMO

INTRODUCTION: Peri-implantitis is a bacterially induced inflammatory disease which affects the hard and soft tissues around a dental implant. Microbial biofilm formation is an important causative factor in peri-implantitis. The aim of this study is to develop an effective multifunctional surface coating for antimicrobial property and to counteract oral biofilm-associated infections via a single polydopamine copper coating (PDAM@Cu) on titanium implant surface to regulate endogenous nitric oxide (NO) generation. METHODS: PDAM@Cu coatings were made with different concentrations of CuCl2 on titanium surfaces with a simple dip coating technique. Coatings were characterised to evaluate Cu concentrations as well as NO release rates from the coatings. Further, salivary biofilms were made on the coatings using Brain Heart Infusion (BHI) media in an anaerobic chamber. Biofilms were prepared with three different mixtures, one of which was saliva only, the second had an addition of sheep's blood, and the third was prepared with NO donors S-nitrosoglutathione (GSNO) and L-glutathione (GSH) in the mixture of saliva and blood to evaluate the effects of endogenously produced NO on biofilms. The effectiveness of coated surfaces on biofilms were assessed using four different methods, namely, crystal violet assay, scanning electron microscopy imaging, 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) metabolic assay, and live/dead staining. RESULTS: NO release rates could be controlled with different Cu concentration in PDAM@Cu coatings. NO generated from the PDAM@Cu coatings effectively induced dispersal of biofilms shown by the reduction in biofilm biomass as well as reduced biofilm attachment in samples prepared with blood and NO donors. Cu ions released from the PDAM@Cu coatings resulted in killing of the dispersed bacteria, which was evidenced by the live/dead cell staining and reduced metabolic activity noted from the XTT assay. In contrast, samples prepared with saliva showed no significant reduction in biofilms, indicating the important effect of endogenously generated NO on biofilm dispersal. CONCLUSION: In conclusion, PDAM@Cu coatings with NO generating surfaces have a dual anti-biofilm function, with a synergistic effect on biofilm dispersal from regulated NO generation and bactericidal effects from Cu ions from the coatings.


Assuntos
Cobre , Óxido Nítrico , Animais , Biofilmes , Materiais Revestidos Biocompatíveis/farmacologia , Cobre/farmacologia , Homicídio , Indóis , Polímeros , Ovinos , Propriedades de Superfície , Titânio/farmacologia
14.
Mater Sci Eng C Mater Biol Appl ; 129: 112392, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34579911

RESUMO

Infections by the gram-negative bacterium Pseudomonas aeruginosa are on the rise, and its antibiotic resistance is a tough challenge for clinical therapeutics worldwide. Therefore, it is an urgent to find alternative antibiotics that possess preferable bactericidal efficiency and are safer than silver (Ag) nanoparticles (Ag NPs). Here, we synthesized small palladium@copper (Pd1.9Cu) alloy NPs with preferable antibacterial functions. We also used a bacteria-infected skin wound mouse model to confirm the sterilization effect of Pd1.9Cu NPs. Pd1.9Cu NPs killed P. aeruginosa at a low concentration, displaying a more powerful bactericidal effect than Ag NPs in vitro. In addition, Pd1.9Cu NPs broke through the bacterial membrane, leading to DNA fragmentation and leakage of genomic DNA and proteins. The underlying mechanism was to trigger the burst of intracellular reactive oxygen species generation and accelerated ion release (Cu and Pd). Pd1.9Cu NPs were also more capable of disinfection than Ag NPs and ceftazidime in vivo, promoting speedy wound recovery. Simultaneously, the biocompatibility of Pd1.9Cu NPs was satisfactory both in vitro and in vivo. These results show that Pd1.9Cu NPs are a promising nanomedicine to treat P. aeruginosa infection.


Assuntos
Nanopartículas Metálicas , Pseudomonas aeruginosa , Animais , Antibacterianos/farmacologia , Cobre/farmacologia , Nanopartículas Metálicas/toxicidade , Camundongos , Paládio , Prata/farmacologia
15.
Cells ; 10(9)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34571908

RESUMO

The critical function of ferroportin (Fpn) in maintaining iron homeostasis requires complex and multilevel control of its expression. Besides iron-dependent cellular and systemic control of Fpn expression, other metals also seem to be involved in regulating the Fpn gene. Here, we found that copper loading significantly enhanced Fpn transcription in an Nrf2-dependent manner in primary bone-marrow-derived macrophages (BMDMs). However, prolonged copper loading resulted in decreased Fpn protein abundance. Moreover, CuCl2 treatment induced Fpn expression in RAW 264.7 macrophages at both the mRNA and protein level. These data suggest that cell-type-specific regulations have an impact on Fpn protein stability after copper loading. Transcriptional suppression of Fpn after lipopolysaccharide (LPS) treatment contributes to increased iron storage inside macrophages and may result in anemia of inflammation. Here, we observed that in both primary BMDMs and RAW 264.7 macrophages, LPS treatment significantly decreased Fpn mRNA levels, but concomitant CuCl2 stimulation counteracted the transcriptional suppression of Fpn and restored its expression to the control level. Overall, we show that copper loading significantly enhances Fpn transcription in macrophages, while Fpn protein abundance in response to CuCl2 treatment, depending on macrophage type and factors specific to the macrophage population, can influence Fpn regulation in response to copper loading.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Cobre/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase , Ferro/metabolismo , Macrófagos/efeitos dos fármacos , Animais , Proteínas de Transporte de Cátions/genética , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos
16.
Int J Mol Sci ; 22(18)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34575991

RESUMO

In this study, we investigated the anti-pseudomonal activity of cupric ions (Cu2+), strawberry furanone (HDMF), gentamicin (GE), and three lytic Pseudomonas aeruginosa bacteriophages (KT28, KTN4, LUZ19), separately and in combination. HDMF showed an anti-virulent effect but only when applied with Cu2+ or GE. GE, at a sub-minimal inhibitory concentration, slowed down phage progeny production due to protein synthesis inhibition. Cu2+ significantly reduced both the bacterial cell count and the number of infective phage particles, likely due to its genotoxicity or protein inactivation and cell membrane disruption effects. Furthermore, Cu2+'s probable sequestration by phage particles led to the reduction of free toxic metal ions available in the solution. An additive antibacterial effect was only observed for the combination of GE and Cu2+, potentially due to enhanced ROS production or to outer membrane permeabilization. This study indicates that possible interference between antibacterial agents needs to be carefully investigated for the preparation of effective therapeutic cocktails.


Assuntos
Cobre/farmacologia , Furanos/farmacologia , Gentamicinas/farmacologia , Infecções por Pseudomonas/terapia , Fagos de Pseudomonas/metabolismo , Pseudomonas aeruginosa , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/virologia
17.
PLoS One ; 16(9): e0257800, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582496

RESUMO

Copper is prevalent in coastal ecosystems due to its use as an algaecide and as an anti-fouling agent on ship hulls. Alteromonas spp. have previously been shown to be some of the early colonizers of copper-based anti-fouling paint but little is known about the mechanisms they use to overcome this initial copper challenge. The main models of copper resistance include the Escherichia coli chromosome-based Cue and Cus systems; the plasmid-based E. coli Pco system; and the plasmid-based Pseudomonas syringae Cop system. These were all elucidated from strains isolated from copper-rich environments of agricultural and/or enteric origin. In this work, copper resistance assays demonstrated the ability of Alteromonas macleodii strains CUKW and KCC02 to grow at levels lethal to other marine bacterial species. A custom database of Hidden Markov Models was designed based on proteins from the Cue, Cus, and Cop/Pco systems and used to identify potential copper resistance genes in CUKW and KCC02. Comparative genomic analyses with marine bacterial species and bacterial species isolated from copper-rich environments demonstrated that CUKW and KCC02 possess genetic elements of all systems, oftentimes with multiple copies, distributed throughout the chromosome and mega-plasmids. In particular, two copies of copA (the key player in cytoplasmic detoxification), each with its own apparent MerR-like transcriptional regulator, occur on a mega-plasmid, along with multiple copies of Pco homologs. Genes from both systems were induced upon exposure to elevated copper levels (100 µM- 3 mM). Genomic analysis identified one of the merR-copA clusters occurs on a genomic island (GI) within the plasmid, and comparative genomic analysis found that either of the merR-copA clusters, which also includes genes coding for a cupredoxin domain-containing protein and an isoprenylcysteine methyltransferase, occurs on a GI across diverse bacterial species. These genomic findings combined with the ability of CUKW and KCC02 to grow in copper-challenged conditions are couched within the context of the genome flexibility of the Alteromonas genus.


Assuntos
Alteromonas/crescimento & desenvolvimento , Organismos Aquáticos/microbiologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Alteromonas/efeitos dos fármacos , Alteromonas/genética , Alteromonas/isolamento & purificação , Cromossomos Bacterianos/genética , Cobre/farmacologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Cadeias de Markov , Plasmídeos/genética , Análise de Sequência de RNA , Sequenciamento Completo do Genoma
18.
J Biomed Nanotechnol ; 17(7): 1435-1447, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446146

RESUMO

Titanium (Ti) and its alloys are widely used in bone surgery by virtue of their excellent mechanical properties and good biocompatibility; however, complications such as loosening and sinking have been reported post-implantation. Herein we deposited a copper-cobalt (Cu-Co) co-doped titanium dioxide (TUO) coating on the surface of Ti implants by microarc oxidation. The osteogenic and antimicrobial properties of the coating were evaluated by in vitro experiments, and we also assessed ß-catenin expression levels on different sample surfaces. Our results revealed that the coating promoted the adhesion, proliferation, and differentiation of MG63 osteoblasts, and TUO coating promoted ß-catenin expression; moreover, the proliferation of Staphylococcus aureus was inhibited. To summarize, we report that Cu-Co co-doping can enhance the osteogenic and antibacterial activities of orthopedic Ti implants, leading to potentially improved clinical performance.


Assuntos
Cobre , Titânio , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Cobalto , Cobre/farmacologia , Osteoblastos , Osteogênese , Propriedades de Superfície , Titânio/farmacologia
19.
J Hosp Infect ; 117: 103-110, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34428505

RESUMO

BACKGROUND: Hospital-acquired infections caused by Pseudomonas aeruginosa have been linked to contaminated shower systems in health care. Thermal disinfection, whereby colonized outlets are flushed with existing hot water supplies, is a commonly used method to disinfect contaminated systems. Temperatures of 60°C are recommended for inactivation of P. aeruginosa; however, this is often not achievable at outlets. AIM: To investigate whether thermal disinfection at a suboptimal temperature (58°C) can effectively eradicate planktonic P. aeruginosa and biofilm adherent on copper piping and shower hoses. Exposure times of up to 60 min and efficacy of repeated cycles were evaluated. METHODS: A type culture and an environmental strain of P. aeruginosa isolated from a hospital shower were tested. Planktonic bacteria and biofilm adhered to sections of copper pipe and shower hoses were exposed to water at 58°C for up to 60 min. Biofilms were tested with static water, flushing water and repeated cycles of disinfection. Remaining viable bacteria after disinfection were enumerated. FINDINGS: Planktonic P. aeruginosa remained viable after up to 60 min of thermal disinfection. With static water, biofilm was removed from copper piping after 15 min, but remained viable in shower hoses for up to 60 min. With thermal flushing, biofilm was fully eradicated from copper piping after 2 min, but remained viable on shower hoses. Repeated cycles did not shorten thermal disinfection exposure times. CONCLUSION: Thermal disinfection at 58°C was effective at eliminating biofilm on copper; however, biofilm on shower hoses remained viable after 60 min of exposure.


Assuntos
Cobre , Pseudomonas aeruginosa , Biofilmes , Cobre/farmacologia , Desinfecção , Humanos , Temperatura
20.
Artigo em Inglês | MEDLINE | ID: mdl-34454693

RESUMO

The sodium valproate has been largely used as an anti-epilepsy drug and, recently, as a putative drug in cancer therapy. However, the treatment with sodium valproate has some adverse effects. In this sense, more effective and secure complexes than sodium valproate should be explored in searching for new active drugs. This study aims to evaluate the cytotoxicity of sodium valproate, mixed ternary mononuclear Cu(II) complexes based on valproic acid (VA) with 1,10-phenanthroline (Phen) or 2,2'- bipyridine (Bipy) ligands - [Cu2(Valp)4], [Cu(Valp)2Phen] and [Cu(Valp)2Bipy] - in yeast Saccharomyces cerevisiae, proficient or deficient in different repair pathways, such as base excision repair (BER), nucleotide excision repair (NER), translesion synthesis (TLS), DNA postreplication repair (PRR), homologous recombination (HR) and non-homologous end-joining (NHEJ). The results indicated that the Cu(II) complexes have higher cytotoxicity than sodium valproate in the following order: [Cu(Valp)2Phen] > [Cu(Valp)2Bipy] > [Cu2(Valp)4] > sodium valproate. The treatment with Cu(II) complexes and sodium valproate induced mutations in S. cerevisiae. The data indicated that yeast strains deficient in BER (Ogg1p), NER (complex Rad1p-Rad10p) or TLS (Rev1p, Rev3p and Rad30p) proteins are associated with increased sensitivity to sodium valproate. The BER mutants (ogg1Δ, apn1Δ, rad27Δ, ntg1Δ and ntg2Δ) showed increased sensitivity to Cu(II) complexes. DNA damage induced by the complexes requires proteins from NER (Rad1p and Rad10p), TLS (Rev1p, Rev3p and Rad30p), PRR (Rad6 and Rad18p) and HR (Rad52p and Rad50p) for efficient repair. Therefore, Cu(II) complexes display enhanced cytotoxicity when compared to the sodium valproate and induce distinct DNA lesions, indicating a potential application as cytotoxic agents.


Assuntos
Cobre/farmacologia , Reparo do DNA/efeitos dos fármacos , Preparações Farmacêuticas/administração & dosagem , Fenantrolinas/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Ácido Valproico/farmacologia , DNA/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Ligantes , Mutação/efeitos dos fármacos , Recombinação Genética/efeitos dos fármacos
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