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1.
J Microbiol ; 57(9): 781-794, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452043

RESUMO

The phytopathogenic Burkholderia species B. glumae and B. plantarii are the causal agents of bacterial wilt, grain rot, and seedling blight, which threaten the rice industry globally. Toxoflavin and tropolone are produced by these phytopathogens and are considered the most hostile biohazards with a broad spectrum of target organisms. However, despite their nonspecific toxicity, the effects of toxoflavin and tropolone on bacteria remain unknown. RNA-seq based transcriptome analysis was employed to determine the genome-wide expression patterns under phytotoxin treatment. Expression of 2327 and 830 genes was differentially changed by toxoflavin and tropolone, respectively. Enriched biological pathways reflected the down-regulation of oxidative phosphorylation and ribosome function, beginning with the inhibition of membrane biosynthesis and nitrogen metabolism under oxidative stress or iron starvation. Conversely, several systems such as bacterial chemotaxis, flagellar assembly, biofilm formation, and sulfur/taurine transporters were highly expressed as countermeasures against the phytotoxins. In addition, our findings revealed that three hub genes commonly induced by both phytotoxins function as the siderophore enterobactin, an iron-chelator. Our study provides new insights into the effects of phytotoxins on bacteria for better understanding of the interactions between phytopathogens and other microorganisms. These data will also be applied as a valuable source in subsequent applications against phytotoxins, the major virulence factor.


Assuntos
Antibacterianos/toxicidade , Burkholderia/química , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Doenças das Plantas/microbiologia , Pirimidinonas/toxicidade , Triazinas/toxicidade , Tropolona/toxicidade , Antibacterianos/metabolismo , Burkholderia/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Oryza/microbiologia , Pirimidinonas/metabolismo , Transcriptoma/efeitos dos fármacos , Triazinas/metabolismo , Tropolona/metabolismo
2.
An Acad Bras Cienc ; 91(2): e20180468, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31241699

RESUMO

This study evaluates the antibacterial, cytotoxic activities, and phytochemical composition, of Callistemon citrinus, Hibiscus rosa-sinensis and Plumbago auriculata leaves and flowers, three ornamental plants in Mexico. However, in other countries offers a range of other uses. Ethanol extracts of C. citrinus leaf and flower presented stronger antibacterial activity than the extracts obtained from the other two plants. C. citrinus leaf showed low cytotoxicity (LC50 <600 µg/mL) on the brine shrimp test, whereas the ethanol extracts of H. rosa-sinensis and P. auriculata leaves showed no cytotoxic activity. Flower extracts obtained from the three plants did no exhibit cytotoxicity. GC-MS analysis revealed that the ethanol extract of P. auriculata leaf contained lupeol triterpene and lupeol acetate, neither of them have been previously reported in this genus. Gamma sitosterol was present in the leaf and flower extracts of P. auriculata. Higher contents of linoleic and linolenic acids were found in extracts of H. rosa-sinensis leaves and flowers. The ability of the ethanol extracts of C. citrinus leaves and flowers to inhibit the growth of Gram-positive and Gram-negative bacteria indicates a potentially broad antimicrobial spectrum. Moreover, the absence of cytotoxicity suggests the potential use of this plant to treat microbial infections.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hibiscus/química , Myrtaceae/química , Extratos Vegetais/farmacologia , Plumbaginaceae/química , Animais , Antibacterianos/toxicidade , Artemia/efeitos dos fármacos , México , Testes de Sensibilidade Microbiana , Extratos Vegetais/toxicidade , Testes de Toxicidade
3.
BMC Complement Altern Med ; 19(1): 150, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242939

RESUMO

BACKGROUND: Traditional medicine remedies are commonly used for treatment of diverse ailments including bacterial infections. The activity against resistant bacteria and safety of some remedies sold as anti-infective treatments in market places in Buea, Southwest Cameroon were investigated as potential alternative treatment to counter increasing antibiotic resistance. METHODS: Ten remedies were purchased, their components documented and microbial load estimated. Methanol extracts of the remedies were tested for antibacterial activity by disc diffusion and microdilution. Cytotoxicity was evaluated on monkey kidney epithelial cells (LLC-MK2) while acute oral toxicity was done in BALB/c mice for the bactericidal extract. Extracts were further analysed using phytochemical tests. RESULTS: All the remedies had microbial loads above the acceptable limit of 105 CFU/g. The highest activity was produced by extracts of four remedies (TP 1, 2, 4, 6a, 6b) against all clinical isolates among which three were active against four control strains. Zones of inhibition ranged from 8 to 27 mm. Two of the four extracts produced zones ≥20 mm against multidrug resistant clinical isolates of Citrobacter freundii and Escherichia coli but were less active compared to Gentamycin positive control (P < 0.0001-0.0014). The most active extracts also recorded minimum inhibitory concentrations of 1 to 4 mg/mL. One of them (TP2) was bactericidal against a clinical isolate of methicillin-resistant Staphylococcus aureus with a minimum bactericidal concentration of 8 mg/mL. Extracts of six remedies did not show cytotoxicity and no mortality or adverse effect was recorded in the acute oral toxicity test. Phytochemical screening showed the most active extracts contained relatively high amounts of alkaloids and flavonoids. CONCLUSION: Only four of the eight remedies tested showed activity against multidrug resistant bacteria suggesting some of these remedies may not be effective against bacterial infections. Production and handling methods should be improved and the product quality controlled to ensure biosecurity. The remedies which were both active and non-toxic should be further investigated including in vivo experiments to assess their efficacy.


Assuntos
Antibacterianos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Camarões , Farmacorresistência Bacteriana Múltipla , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Feminino , Humanos , Medicina Tradicional , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais/microbiologia
4.
Eur J Med Chem ; 178: 214-231, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31185412

RESUMO

Discovery of antimicrobial agents with a novel model of action is in urgent need for the clinical management of multidrug-resistant bacterial infections. Recently, we reported the identification of a first-in-class bacterial ribosomal RNA synthesis inhibitor, which interrupted the interaction between the bacterial transcription factor NusB and NusE. In this study, a series of diaryl derivatives were rationally designed and synthesized based on the previously established pharmacophore model. Inhibitory activity against the NusB-NusE binding, circular dichroism of compound treated NusB, antimicrobial activity, cytotoxicity, hemolytic property and cell permeability using Caco-2 cells were measured. Structure-activity relationship and quantitative structure-activity relationship were also concluded and discussed. Some of the derivatives demonstrated improved antimicrobial activity than the hit compound against a panel of clinically important pathogens, lowering the minimum inhibition concentration to 1-2 µg/mL against Staphylococcus aureus, including clinical strains of methicillin-resistant Staphylococcus aureus at a level comparable to some of the marketed antibiotics. Given the improved antimicrobial activity, specific inhibition of target protein-protein interaction and promising pharmacokinetic properties without significant cytotoxicity, this series of diaryl compounds have high potentials and deserve for further studies towards a new class of antimicrobial agents in the future.


Assuntos
Compostos de Anilina/farmacologia , Antibacterianos/farmacologia , Benzilaminas/farmacologia , Ligação Proteica/efeitos dos fármacos , Bases de Schiff/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Compostos de Anilina/toxicidade , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/toxicidade , Proteínas de Bactérias/metabolismo , Benzilaminas/síntese química , Benzilaminas/química , Benzilaminas/toxicidade , Células CACO-2 , Desenho de Drogas , Eritrócitos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/toxicidade , Relação Estrutura-Atividade , Fatores de Transcrição/metabolismo
5.
Bratisl Lek Listy ; 120(6): 429-433, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223023

RESUMO

OBJECTIVE: This study was conducted to evaluate the protective effect of dexmedetomidine on nephrotoxicity and the mechanism of renoprotection following vancomycin-induced nephrotoxicity in rats. METHODS: Thirty-two albino Wistar rats were divided into four groups. The control group received intraperitoneal (IP) physiological saline solution, the vancomycin (VMC) group received IP 200 mg/kg vancomycin, the dexmedetomidine (DEX) group received IP 5 µg/kg dexmedetomidine, and the vancomycin and dexmedetomidine (VMC+DEX) group received IP 200 mg/kg vancomycin followed by IP 5 µg/kg dexmedetomidine 20 min after the vancomycin injection. On the 8th day of the experiment, histopathological and biochemical parameters were assessed. RESULTS: Creatinine levels were significantly higher in VMC and VMC+DEX groups. The endothelin-1 level was significantly higher in VMC group. Nitric oxide levels were statistically lower in VMC and VMC+DEX groups. Histopathologic assessments revealed that the extent of renal damage was significantly higher in group VMC (n = 4 with damage of Grade 3) compared to group VMC+DEX (n = 0 with damage of Grade 3). CONCLUSION: It was determined that dexmedetomidine can reduce the extent of renal damage by preventing the elevation of vasoconstrictor agents (Tab. 2, Fig. 1, Ref. 36).


Assuntos
Lesão Renal Aguda , Agonistas de Receptores Adrenérgicos alfa 2 , Antibacterianos , Dexmedetomidina , Vancomicina , Lesão Renal Aguda/induzido quimicamente , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Antibacterianos/toxicidade , Dexmedetomidina/farmacologia , Ratos , Ratos Wistar , Vancomicina/toxicidade , Vasoconstrição/efeitos dos fármacos
6.
Carbohydr Polym ; 217: 58-68, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31079685

RESUMO

The fruit of Akebia trifoliata var. australis can be consumed as food. However, the peel of this fruit is typically regarded as waste. The application of such waste can create opportunities to produce new and valuable by-products. Herein, we have shown that citric acid extracted pectin (CEP) from Akebia trifoliata var. australis peel has good water solubility and high galacturonic units, which helps reduce AgNO3 into Ag nanoparticles (CEP-AgNPs) through a one-step, eco-friendly process. The resulting CEP-AgNPs showed sustained release of Ag+ and remarkable antibacterial activity. Subsequently, the CEP-AgNPs were processed into a CEP-Ag sponge with excellent water absorption and prolonged water retention properties. The CEP-Ag sponge could support the cell adhesion and proliferation. Most importantly, the sponge effectively facilitated a moist environment with bacterial disinfection capability which accelerated the healing of infected wounds. Thus, CEP-Ag sponge, a sustainable and high value by-product, was obtained from food waste.


Assuntos
Antibacterianos/uso terapêutico , Bandagens , Nanopartículas Metálicas/uso terapêutico , Pectinas/química , Resíduos Sólidos , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Permeabilidade da Membrana Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Frutas/química , Química Verde/métodos , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pectinas/isolamento & purificação , Pectinas/toxicidade , Ranunculales/química , Ratos Sprague-Dawley , Prata/química , Prata/uso terapêutico , Prata/toxicidade , Nitrato de Prata/química , Pele/patologia , Solubilidade , Água/química , Molhabilidade
7.
Sci Total Environ ; 681: 56-65, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31102817

RESUMO

The inhibitory effects of oxytetracycline (OTC) on the anaerobic ammonium oxidation (anammox) performance were relieved by employing bio-augmentation (BA) tactics. However, the recovery mechanism was vague. The response of specific anammox activity (SAA), heme c, functional genes, extracellular polymeric substance (EPS) and antibiotics resistance genes (ARGs) to OTC inhibition and BA aid were traced in the present study. The results indicated that response of SAA, heme c content and functional genes, such as nirS, hzsA and hdh to OTC inhibition were not synchronous. The presence of the tetC, tetG, tetX, and intI1 genes enhanced the resistance of anammox sludge to OTC, thus accelerating the performance recovery when aided by BA. A significant correlation existed between number of anammox 16S rRNA gene copies and protein level in the soluble microbial products (SMP), between tetG gene relative abundance and polysaccharose in SMP and between tetG gene relative abundance and protein in bound EPS (EPSs). In nutshell, the current findings provide the first description of a recovery mechanism regarding OTC-inhibited anammox performance aided by BA based on functional genes and highlights the contribution of ARGs and the self-resistance ability of EPS.


Assuntos
Antibacterianos/toxicidade , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Oxitetraciclina/toxicidade , Matriz Extracelular de Substâncias Poliméricas , RNA Ribossômico 16S , Esgotos
8.
Environ Sci Pollut Res Int ; 26(18): 18662-18673, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31055748

RESUMO

Procaine penicillin (PP) is a ß-lactam antibiotic widely used in human and veterinary medicine. Although PP is detected in surface water, little is known on its effects on aquatic invertebrates. Our aim was to determine the influence of PP on swimming behaviour (track density, swimming speed, turning angle, hopping frequency) and physiological activity (oxygen consumption, heart rate, thoracic limb movement) of a freshwater invertebrate Daphnia magna exposed to PP at concentrations of 11.79 mg/L, 117.9 mg/L and 1179 mg/L for 2 h and 24 h. The results showed no mortality; however, reduction of swimming activity manifested by the decreased track density, swimming speed and turning angle noted in Daphnia exposed to all the concentrations of PP. Increase of oxygen consumption was observed after 2-h exposure; however, decrease of this parameter was found after 24 h. PP also reduced heart rate and thoracic limb movement in a concentration-dependent manner. The results suggest that the antibiotic should not induce mortality; however, it may affect swimming behaviour and physiological parameters of Daphnia magna particularly inhabiting aquaculture facilities with intensive antibiotic treatment. On the basis of the present results, we also suggest higher sensitivity of behavioural and physiological parameters of cladocerans than the commonly used endpoints: mortality or immobilisation and their possible application as a part of early warning systems in monitoring of surface water toxicity.


Assuntos
Antibacterianos/toxicidade , Daphnia/fisiologia , Monitoramento Ambiental , Penicilina G Procaína/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Natação
9.
Environ Sci Pollut Res Int ; 26(18): 18930-18937, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31055743

RESUMO

Antibiotics have a wide application range in human and veterinary medicines. Being designed for pharmacological stability, most antibiotics are recalcitrant to biodegradation after ingestion and can be persistent in the environment. Antibiotic residues have been detected as contaminants in various environmental compartments where they cause human and environmental threats, notably with respect to the potential emergence and proliferation of antibiotic-resistant bacteria. An important component of managing environmental risk caused by antibiotics is to understand exposure of soil and water resources to their residues. One challenge is to gain knowledge on the fate of antibiotics in the ecosystem along the soil-water continuum, and on the collateral impact of antibiotics on environmental microorganisms responsible for crucially important ecosystem functions. In this context, the ANTIBIOTOX project aims at studying the environmental fate and impact of two antibiotics of the sulfonamide class of antibiotics, sulfamethazine (SMZ), and sulfamethoxazole (SMX).


Assuntos
Antibacterianos/análise , Farmacorresistência Bacteriana , Microbiota/efeitos dos fármacos , Poluentes do Solo/análise , Poluentes da Água/análise , Antibacterianos/toxicidade , Biodegradação Ambiental , Farmacorresistência Bacteriana/efeitos dos fármacos , Ecotoxicologia , Humanos , Medição de Risco , Solo/química , Microbiologia do Solo , Poluentes do Solo/toxicidade , Água/química , Microbiologia da Água , Poluentes da Água/toxicidade
10.
Environ Pollut ; 251: 257-263, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31082610

RESUMO

Biological tests with plant seeds have been adopted in many studies to investigate the phytotoxicity of pollutants to facilitate the control of risks and remain to be optimized. In this work, the experiment with a small sample size (Experiment 1) and the experiment with a large one (Experiment 2) were designed to study the effect of tetracycline (TC) on Chinese cabbage (Brassica rapa L.) at seed germination and radicle elongation stages. At the former stage, germination number data were obtained to analyze the germination energy (GE) and to judge the probability of the number of germinated seeds (Pn) by the binomial distribution model in Experiment 1. While germination time-to-number data were obtained to analyze the mean time to germination (MGT), the estimate of mean time to germination (EMGT) by survival analysis method, the time to germination for 50% of total seeds (T50) and the germination rate (GR) besides GE in Experiment 2. At the latter stage, the data of radicle length (RL) were obtained in all the experiments and the influence from the former stage on this stage was excluded in Experiment 2 but not in Experiment 1. Results showed that TC had universal adverse effects on the latter stage but not on the former stage in the experiments. Considering the availability of germination data for statistical analysis and the robustness of RL data, the methods adopted in Experiment 2 were more feasible than those in Experiment 1. In addition, Chinese cabbage seeds with medium size have the character of rapid germination compared with the commonly used crop species and can be used to shorten the experimental cycle to study the responses of seeds to pollutants to evaluate the phytotoxicity. We introduced survival analysis method to analyze the germination time-to-number data obtained in seed germination test to evaluate the phytotoxicity of tetracycline.


Assuntos
Antibacterianos/toxicidade , Germinação/efeitos dos fármacos , Tetraciclina/toxicidade , Brassica/efeitos dos fármacos , Sementes/efeitos dos fármacos
11.
Carbohydr Polym ; 216: 25-35, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047065

RESUMO

The unique physicochemical and functional characteristics of starch-based biomaterials and wound dressings have been proposed for several biomedical applications. Film dressings of cornstarch/hyaluronic acid/ ethanolic extract of propolis (CS/HA/EEP) were prepared by solvent-casting and characterized by attenuated total reflectance/Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography/mass spectrometry, light transmission, opacity measurements, EEP release, equilibrium swelling, and in vitro and in vivo evaluations. The CS/HA/0.5%EEP film dressing exhibited higher antibacterial activity against Staphylococcus aureus (2.08 ± 0.14 mm), Escherichia coli (2.64 ± 0.18 mm), and Staphylococcus epidermidis (1.02 ± 0.15 mm) in comparison with the CS, CS/HA, and CS/HA/0.25%EEP films. Also, it showed no cytotoxicity for the L929 fibroblast cells. This wound dressing could effectively accelerate the wound healing process at Wistar rats' skin excisions. These results indicate that enrichment of cornstarch wound dressings with HA and EEP can significantly enhance their potential efficacy as wound dressing material.


Assuntos
Antibacterianos/farmacologia , Ácido Hialurônico/química , Curativos Oclusivos , Própole/farmacologia , Amido/química , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Galinhas , Escherichia coli/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Ácido Hialurônico/toxicidade , Hidrólise , Muramidase/química , Própole/química , Própole/toxicidade , Ratos Wistar , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Amido/toxicidade , Cicatrização/efeitos dos fármacos
12.
Sci Total Environ ; 681: 350-364, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31117016

RESUMO

This work deals with the fabrication of metallosurfactants derived cobalt oxide and hydroxide nanosuspensions (Ns) by microemulsion method and their antimicrobial, cytotoxic, genotoxic, antioxidant and cytostatic activity have been investigated. The methodology used is environmentally compliant as no external reducing agent was used. Three metallosurfactants i.e. CoCTAC (Bishexadecyltrimethylammonium cobalt tetrachloride), CoDDA (Bisdodecylamine cobalt dichloride) and CoHEXA (bishexadecylamine cobalt dichloride) were used. Co-metallosurfactants were synthesized, characterized and were utilized for the preparation of mixed microemulsion to yield nanosuspensions. Nanoparticles prepared were characterized using Transmission electron microscopy (TEM), Field Emission Scanning Electron Microscope (FESEM), Energy Dispersive X-ray Spectroscopy (EDS), X-ray Diffraction (XRD), UV-vis spectroscopy and Zeta potential. The nanoparticles were found to be spherical, with size range 1-5 nm, for all the three precursors. Further, their cytotoxicity, genotoxicity, and antimicrobial activity were investigated against Staphylococcus aureus (S. aureus). To evaluate these activities, techniques such as gram staining method, agar well diffusion, and colony forming unit count (CFU) were utilized. From all these experiments it was confirmed that CoCTAC Ns has maximum antimicrobial activity against multiple medicine resistant S. aureus. Circular dichroism and gel electrophoresis also validated the vigorous genotoxic effect of CoCTAC Ns. The antimicrobial activity trend investigated from CFU experiment was CoCTAC Ns (2 × 105 CFU/mL) > CoDDA Ns (17 × 105 CFU/mL) > CoHEXA Ns (46.5 × 105 CFU/mL). FESEM authenticated the effect of Co Ns on the morphology of S. aureus. Cell shrinkage, formation of holes, change of morphology, and cell wall rupturing was observed for all three cases but most significant antibacterial activity was noted for the case of CoCTAC Ns. In addition, antiproliferative activity was also examined against HepG2 cells (human liver cancer cell line) and HEK293 cells (human embryonic kidney cell line). After 70% confluency of cells, cobalt oxide/hydroxide Ns were added by diluting the nanosuspension in 0.2, 0.4, 0.5, and 0.8% V/V ratio to check the cell viability.


Assuntos
Antibacterianos/toxicidade , Nanopartículas Metálicas/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Tensoativos/toxicidade , Cobalto/toxicidade , Óxidos/toxicidade
13.
Ecotoxicol Environ Saf ; 178: 146-158, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31002969

RESUMO

Animal manure or bio-solids used as fertilizers are the main routes of antibiotic exposure in the agricultural land, which can have immense detrimental effects on plants. Sulfadiazine (SDZ), belonging to the class of sulfonamides, is one of the most detected antibiotics in the agricultural soil. In this study, the effect of SDZ on the growth, changes in antioxidant metabolite content and enzyme activities related to oxidative stress were analysed. Moreover, the proteome alterations in Arabidopsis thaliana roots in response to SDZ was examined by means of a combined iTRAQ-LC-MS/MS quantitative proteomics approach. A dose-dependent decrease in leaf biomass and root length was evidenced in response to SDZ. Increased malondialdehyde content at higher concentration (2 µM) of SDZ indicated increased lipid peroxidation and suggest the induction of oxidative stress. Glutathione levels were significantly higher compared to control, whereas there was no increase in ascorbate content or the enzyme activities of glutathione metabolism, even at higher concentrations. In total, 48 differentially abundant proteins related to stress/stimuli response followed by transcription and translation, metabolism, transport and other functions were identified. Several proteins related to oxidative, dehydration, salinity and heavy metal stresses were represented. Upregulation of peroxidases was validated with total peroxidase activity. Pathway analysis provided an indication of increased phenylpropanoid biosynthesis. Probable molecular mechanisms altered in response to SDZ are highlighted.


Assuntos
Antibacterianos/toxicidade , Arabidopsis/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteoma/metabolismo , Poluentes do Solo/toxicidade , Sulfadiazina/toxicidade , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Fertilizantes/análise , Esterco/análise , Proteômica/métodos , Solo/química
14.
Sci Total Environ ; 673: 357-366, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-30991325

RESUMO

Gut microbiota make an important contribution to the health of soil invertebrates. Many studies have focused on effects of antibiotics on soil invertebrates. Influence from antibiotics on the gut microbiota of non-target soil fauna is rarely reported and the abundance of antibiotics resistance genes (ARGs) in the gut is poorly understood. Here, 10 µg·g-1 of oxytetracycline (OTC) (environmentally relevant concentration) was added in soil, used Enchytraeus crypticus as soil model worm was tested for the response to oxytetracycline. The results showed that although soil OTC exposure did not cause a change in E. crypticus growth, mortality or reproduction, it did result in bioaccumulation of OTC in E. crypticus body tissues. The OTC treatment induced a shift in the composition and diversity of the gut microbiota of E. crypticus when compared to the control treatment. Specifically, the relative abundance of Proteobacteria declined significantly from 52.2% to 32.4% after OTC exposure (P = 0.028), but the relative abundance of Planctomycetes was significantly elevated from 28.1% to 45.8% (P = 0.002). It is noteworthy that soil OTC exposure significantly enhanced the abundance and number of tetracycline-related ARGs in the E. crypticus gut. These results suggest that change in E. crypticus gut microbiota has potential as an indicator of soil antibiotic pollution, and E. crypticus gut may act as a receiver and mediator of ARGs resulting from soil antibiotic pollution.


Assuntos
Antibacterianos/toxicidade , Resistência Microbiana a Medicamentos/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Oxitetraciclina/toxicidade , Microbiologia do Solo , Poluentes do Solo/toxicidade , Animais , Genes Bacterianos , Oligoquetos
15.
Eur J Med Chem ; 174: 16-32, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31022550

RESUMO

Intrinsic resistance in Pseudomonas aeruginosa, defined by chromosomally encoded low outer membrane permeability and constitutively over-expressed efflux pumps, is a major reason why the pathogen is refractory to many antibiotics. Herein, we report that heterodimeric rifampicin-tobramycin conjugates break this intrinsic resistance and sensitize multidrug and extensively drug-resistant P. aeruginosa to doxycycline and chloramphenicol in vitro and in vivo. Tetracyclines and chloramphenicol are model compounds for bacteriostatic effects, but when combined with rifampicin-tobramycin adjuvants, their effects became bactericidal at sub MIC levels. Potentiation of tetracyclines correlates with the SAR of this class of drugs and is consistent with outer membrane permeabilization and efflux pump inhibition. Overall, this strategy finds new uses for old drugs and presents an avenue to expand the therapeutic utility of legacy antibiotics to recalcitrant pathogens such as P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Cloranfenicol/farmacologia , Doxiciclina/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Rifampina/farmacologia , Tobramicina/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/toxicidade , Proteínas da Membrana Bacteriana Externa/metabolismo , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Células HEK293 , Células Hep G2 , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mariposas , Rifampina/análogos & derivados , Rifampina/síntese química , Rifampina/toxicidade , Suínos , Tobramicina/análogos & derivados , Tobramicina/síntese química , Tobramicina/toxicidade
16.
Biointerphases ; 14(2): 021004, 2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947504

RESUMO

Effective use of medical device implants is often hindered by infection, which may cause the device to be rejected from the body and seriously endanger health. Such infections are often a result of biofilm formation or microbial colonies collecting on a surface. Therefore, a challenge in the medical field is to mitigate the impact of biofilm formation in order to save thousands of lives and millions of healthcare dollars annually. The proposed strategy is to target the attachment phase of the biofilm lifecycle to try to prevent the formation of antimicrobial resistant biofilms. Prevention of bacterial attachment may be induced through the introduction of nitric oxide (NO), a small biological signaling molecule known for its antibacterial properties. NO may be delivered via release from a donating molecule incorporated in the polymer composing the medical device. The NO donor S-nitrosoglutathione (GSNO) was utilized in this study because it is a relatively stable small molecule that naturally exists in the body, therefore negating possible adverse reactions when it is introduced to the body. Tygon®, a polymer commonly found in Food and Drug Administration approved medical devices such as catheters, was utilized as a platform for the inhibition of biofilms. To study the necessary amount of released NO needed to cause a reduction in attachment across varying strains, different concentrations of GSNO were applied. Two Gram-negative (Pseudomonas aeruginosa and Acinetobacter baumannii) and two Gram-positive species (Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus), all strong biofilm formers listed as urgent threats by the Center for Disease Control, illustrated different responses to NO. Gram-positive species showed a decrease in viability over 80% with an average total NO release of 2.01 ± 2.11 × 10 - 4 µmols, while Gram-negative response was less, with viability decreasing to 38% (P. aeruginosa) and 71% (A. baumannii) with 1.25 ± 1.63 × 10-4 µmols NO. Further studies utilizing glutathione surface roughness controls highlight that increasing the surface roughness of the polymer platform produces no statistically significant difference in viability compared to the Tygon-only negative control in all strains except P. aeruginosa. Developing a quantitative understanding of how NO release and platform surface roughness impact biofilm attachment across Gram strains is key to reducing the incidence and impact of medical device associated infections.


Assuntos
Antibacterianos/toxicidade , Biofilmes/efeitos dos fármacos , Microbiologia Ambiental , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Óxido Nítrico/toxicidade , Propriedades de Superfície , Biofilmes/crescimento & desenvolvimento , Equipamentos e Provisões/microbiologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Viabilidade Microbiana/efeitos dos fármacos , S-Nitrosoglutationa/toxicidade
17.
Sci Total Environ ; 676: 31-39, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31029898

RESUMO

Chlorine is widely used as a drinking water disinfectant to ensure water security. However, the transformation mechanisms of its degradation of emerging pollutants within the water distribution system (WDS) is insufficiently understood. Thus, the kinetics, degradation byproducts, and toxicity of the chlorination of enoxacin (ENO, a type of emerging pollutant) were explored in a pilot-scale WDS for the first time. It was found that the chlorination rate of ENO was higher in deionized water (DW) than in the pilot-scale WDS, and the degradation followed second-order kinetics in DW. The degradation efficiency was found to be sensitive to pH, and was highest at a pH of 7.4. The chlorination rate of ENO increased with increasing temperature in both DW and WDS. For different pipe materials, the relative performance of ENO chlorination efficiency followed the order of steel pipe > ductile iron pipe > polyethylene (PE) pipe. Seven intermediates were identified during ENO chlorination, and the primary oxidation reaction involved the cleavage of the piperazine group. Finally, it was found that the potential for chlorine toxicity in treated drinking water in the presence of ENO is higher than it is without this pollutant.


Assuntos
Antibacterianos/química , Cloro/química , Água Potável/química , Enoxacino/química , Poluentes Químicos da Água/química , Purificação da Água , Antibacterianos/análise , Antibacterianos/toxicidade , Enoxacino/análise , Enoxacino/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
18.
Int J Antimicrob Agents ; 53(6): 838-843, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928682

RESUMO

The alarming burden of antibiotic resistance in nosocomial pathogens warrants the discovery and development of new and effective antimicrobial compounds. Small cationic antimicrobial peptides seem to be a promising therapeutic alternative to fight multi-drug resistance. This study investigated the in-vitro potential of a previously reported lantibiotic, paenibacillin, from the clinical perspective. An antimicrobial peptide, M152-P4, was isolated, purified and characterized from a mud isolate, and its susceptibility was determined in clinical isolates of Staphylococcus aureus and Enterococcus spp. Time-kill kinetics, resistance, probable mode of action, haemolytic activity and mammalian cytotoxicity were investigated. M152-P4 was identified as paenibacillin based on mass spectroscopy data, amino acid analysis and biosynthetic gene cluster analysis. It had potent antibacterial activity against the Gram-positive pathogens tested, with minimum inhibitory concentrations from 0.1 to 1.56 µM. It appeared very challenging for S. aureus to develop resistance to this compound. Also, paenibacillin penetrated the outer layer of bacteria, and depolarized the membrane completely by creating pores in the plasma membrane with better potential than nisin. Paenibacillin showed no haemolysis up to 60 µM, and the half maximal inhibitory concentration on mammalian cell lines was >100 µM. These results highlight the excellent antibacterial properties of paenibacillin in clinically relevant pathogens. It is stable in the presence of serum, and non-haemolytic and non-cytotoxic even above the therapeutic concentration. Further research efforts regarding toxicity and in-vivo efficacy are necessary to develop paenibacillin as a next-generation therapeutic drug to overcome multi-drug resistance in Gram-positive pathogens.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bacteriocinas/farmacologia , Enterococcus/efeitos dos fármacos , Paenibacillus/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/toxicidade , Bacteriocinas/química , Bacteriocinas/isolamento & purificação , Bacteriocinas/toxicidade , Vias Biossintéticas/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Farmacorresistência Bacteriana , Humanos , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Família Multigênica , Paenibacillus/classificação , Paenibacillus/isolamento & purificação , Análise de Sequência de Proteína , Esgotos/microbiologia
19.
J Appl Microbiol ; 127(1): 59-67, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31006174

RESUMO

AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound. METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin. CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.


Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Gengibre/química , Bactérias Gram-Positivas/efeitos dos fármacos , Antibacterianos/efeitos adversos , Antibacterianos/toxicidade , Bornéu , Morte Celular/efeitos dos fármacos , Células Cultivadas , Curcumina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Permeabilidade/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia
20.
Environ Sci Pollut Res Int ; 26(15): 15481-15495, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30937749

RESUMO

Due to their worldwide use and environmental persistence, antibiotics are frequently detected in various aquatic compartments. Their toxic properties raise environmental concerns to non-target organisms. Histopathology data is frequently applied in ecotoxicology studies to assess the effects of different classes of environmental stressors in fish, including antibiotics. Tissue alterations in gills and liver of gilthead seabream (Sparus aurata) individuals acutely (96 h) and chronically (28 days) exposed to environmentally relevant concentrations of the antibiotics erythromycin (ERY: 0.0002-200 µg/L) and oxytetracycline (OTC: 0.0004-400 µg/L), including a control non-exposed group, were evaluated. Several disorders (circulatory, regressive, progressive, and inflammatory) were observed in both organs of all exposed animals. The hereby obtained data showed a higher and significant increase in gill histopathological index of organisms acutely exposed to ERY and of those chronically exposed to OTC. In terms of categorical lesions, only a significant increase of regressive and progressive alterations occurred in gills after chronic exposure to OTC. For the liver, a significant increase in pathological index was also detected, as well as regressive changes, after chronic exposure to OTC. Furthermore, the present study indicates that most of the changes observed in gills and liver were of mild to moderate severity, which might be adaptive or protective, non-specific, and mostly reversible. Despite being observed, irreversible lesions were not significant in any of the fish organs analyzed. Although there were histological changes, gill apparatus was considered still functionally normal, as well as liver tissue, not supporting the occurrence of severe toxicity. In general, the observed histological changes were not stressor-specific, and toxicological mechanistic explanations for the alterations observed in gills and liver are presented. The obtained data showed that histopathological biomarkers can be successfully applied in ecotoxicological studies, evidencing their relevance, responsivity, and complementarity to other biochemical biomarker-based approaches.


Assuntos
Antibacterianos/toxicidade , Eritromicina/toxicidade , Brânquias/efeitos dos fármacos , Fígado/efeitos dos fármacos , Oxitetraciclina/toxicidade , Dourada/fisiologia , Animais , Antibacterianos/efeitos adversos , Biomarcadores
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