RESUMO
Staphylococcus aureus is a bacterium responsible for resistance to multiple drugs and the efflux system is widely studied among the resistance mechanisms developed by this species. The present study evaluates the inhibition of the MepA efflux pump by thiadiazine-derived compounds. For this purpose, thiadiazine-derived compounds (IJ-14 to IJ-20) were tested against S. aureus K2068 strains. Microdilution tests were initially conducted to assess the Minimum Inhibitory Concentration (MIC) of the compounds and their efflux pump inhibition activity. In addition, fluorimetry tests were performed using BrEt emission and tests were conducted to inhibit the expression of the mepA gene. This involved comparing the bacterial gene expression with the antibiotic alone to the gene expression after combining compounds (IJ-17 and IJ-20) with the antibiotic. Furthermore, membrane permeability assessment tests and in silico molecular docking tests were performed. It was observed that the IJ17 and IJ20 compounds exhibited direct activity against the tested strain. The IJ17 compound produced significant results in the gene inhibition tests, which was also evidenced through the membrane permeability alteration test. These findings suggest that thiadiazine-derived compounds have promising effects against one of the main resistance mechanisms, with the IJ17 compound presenting observable mechanisms of action.
RESUMO
The objective of this work was to evaluate the inhibitory effect of quercetin on S. aureus Efflux Pumps. The MIC of Quercetin was evaluated through the broth microdilution method, as well as the Efflux Pump inhibition assay through the method of reducing the antibiotic minimum inhibitory concentration as well as that of ethidium bromide. The in silico approach through bioinformatics was performed to demonstrate the molecular mechanism of interaction of the substrate and the binding cavity. The Quercetin inhibition concentration was not clinically relevant. With respect to the reversal of bacterial resistance effect by efflux pump inhibition, this effect was observed with the strains carrying the TetK and NorA pumps. Regarding the interaction between the Quercetin complex and the NorA pump, the extra stability was provided by hydrogen bonds produced by the hydroxyl group.
Assuntos
Antibacterianos/uso terapêutico , Quercetina/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Quercetina/farmacologiaRESUMO
The Aedes aegypti is responsible for the transmission of arboviruses, which compromise public health. In the search for synthetic product alternatives, essential oils (OEs) have been highlighted by many researchers as natural insecticides. This systematic review (SR) was performed according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and its objective was to evaluate studies addressing OEs with larvicidal properties against Ae. aegypti, through electronic database searches (Pubmed, Science Direct and Scielo), covering an overview of the plant sources OEs, which plant parts were used, the extraction methods, analytical techniques, major and/or secondary constituents with greater percentages, as well as the LC50s responsible for larval mortality. Following study analysis, plants distributed across 32 families, 90 genera and 175 species were identified. The Lamiaceae, Myrtaceae, Piperaceae, Asteraceae, Rutaceae, Euphorbiaceae and Lauraceae families obtained the highest number of species with toxic properties against larvae from this vector. Practically all plant parts were found to be used for OE extraction. Hydrodistillation and steam distillation were the main extraction methods identified, with GC-MS/GC-FID representing the main analytical techniques used to reveal their chemical composition, especially of terpene compounds. In this context, OEs are promising alternatives for the investigation of natural, ecologically correct and biodegradable insecticides with the potential to be used in Ae. aegypti control programs.
Assuntos
Aedes , Inseticidas , Óleos Voláteis , Animais , Humanos , Larva , Mosquitos Vetores , Óleos Voláteis/farmacologia , Óleos de PlantasRESUMO
The objective of this work was to evaluate the antioxidant, metal chelating and cytoprotective activity of the Eugenia jambolana Lam. extract, as well as of its flavonoid and tannic fractions, against the action of Mercury Chloride (HgCl2). Flavonoids were quantified and an LC-MS chromatographic analysis was performed to identify secondary metabolites. Fe2+ and Fe3+ chelation tests and antioxidant activity were carried out using the FRAP method. Microbiological tests were performed by microdilution to determine the Minimum Inhibitory Concentration (MIC). From these results the Minimum Bactericidal (MBC) and Minimum Fungicide Concentration (MFC) were evaluated. The allelopathy and cytoprotection assays were performed using eukaryotic and prokaryotic models. The results revealed the presence of phenolic acids and flavonoids in the E. jambolana extract and fractions. The sub-allelopathic concentration (64⯵g/mL) was used and the results demonstrated the E. jambolana potential cytoprotective effect against mercury chloride.
Assuntos
Produtos Biológicos/química , Cloreto de Mercúrio/toxicidade , Syzygium/química , Alelopatia , Anti-Infecciosos/química , Antioxidantes/química , Citoproteção , Flavonoides/química , Lactuca/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Extratos Vegetais/químicaRESUMO
The present study had as its objective to verify the Psidium guajava var. Pomifera L. chelating, antioxidant and cytoprotective effects against mercury and aluminum. The ethanolic extract, tannic and flavonoid fractions were subjected to LC-MS analysis. The Ferric Reducing Antioxidant Power (FRAP) and ferric ion reduction demonstrated a present antioxidant activity. The fungicidal and bactericidal activity of these metals were established. After determining the sub-allelopathic doses, germination tests using Lactuca sativa were performed. Quercetin and its derivatives were the main compounds identified in the extract and the fractions. Mercury chloride significantly reduced the bactericidal effect of the flavonoid fraction (pâ¯<â¯0.001). None of the fractions were cytoprotective against mercury or aluminum in the fungal model assays. Using a sub-allelopathic concentration (64⯵g/mL), the ethanolic extract, flavonoid and tannic fractions were found to be cytoprotective against aluminum for radicles, however only the tannic fraction was cytoprotective for caulicles. These data suggest that natural P. guajava products are promising cytoprotective compound sources. This activity may be related to the antioxidant effect of secondary metabolites, mainly flavonoids. Our results point to a potential for environmental intervention product and technique development aimed at mitigating contamination by toxic metals such as mercury and aluminum.
Assuntos
Antioxidantes/química , Flavonoides/química , Metais Pesados/toxicidade , Psidium/química , Antioxidantes/análise , Metais Pesados/análiseRESUMO
This study aimed to verify the chelating, antioxidant and cytoprotective activities of Psidium brownianum Mart. Ex DC against mercury and aluminum. The ethanolic extract, as well as the tannic and flavonoid fractions, were prepared and subjected to liquid chromatography-mass spectrometry analysis. Ferric ion reduction and antioxidant activity measurement using the FRAP method were performed with P. brownianum. After determining the sub-allelopathic doses, germination tests using Lactuca sativa (lettuce) seeds were performed. The main compounds identified in the extract and fractions were: quercetin and its derivatives; myricetin and its derivatives; gallic acid; ellagic acid; quinic acid and gallocatechin. The Minimum Inhibitory Concentration (MIC) for all samples wereâ¯≥â¯1024⯵g/mL. The flavonoid fraction in association with mercury chloride demonstrated cytoprotection (pâ¯<â¯0.001). The sub-allelopathic concentration used was 64⯵g/mL. The extract and fractions were cytoprotective for radicles and caulicles when assayed in association with mercury and against aluminum for radicles. This suggests that the P. brownianum extract and its fractions present cytoprotective activity, possibly related to the antioxidant effect of secondary metabolites, especially flavonoids.
Assuntos
Cloreto de Alumínio/toxicidade , Antioxidantes/farmacologia , Quelantes/farmacologia , Cloreto de Mercúrio/toxicidade , Extratos Vegetais/farmacologia , Psidium , Alelopatia , Antioxidantes/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Quelantes/química , Cromatografia Líquida , Citoproteção , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Flavonoides/análise , Flavonoides/farmacologia , Germinação/efeitos dos fármacos , Ferro/química , Lactuca/efeitos dos fármacos , Lactuca/crescimento & desenvolvimento , Espectrometria de Massas , Extratos Vegetais/químicaRESUMO
This study was carried out to test the essential oil from C. ambrosioides leaves and its main constituent, α-Terpinene, in an antibacterial activity assay. As well, it was evaluated ability reduce resistance to norfloxacin and ethidium bromide was compared the Staphylococcus aureus 1199B whith 1199 wild type strain. The MIC of the C. ambrosioides essential oil and α-Terpinene were determined by microdilution method. The MIC of the essential oil and α-Terpinene presented a valueâ¯≥â¯1024⯵g/mL. However, when associated with antibacterials, the essential oil from C. ambrosioides leaves significantly reduced the MIC of antibiotics and ethidium bromide, characterizing an efflux pump inhibition. The C. ambrosioides essential oil, despite having no direct antibacterial activity against the S. aureus 1199B strain, showed a potentiating action when associated with antibacterial agents, this being attributed to an inhibition of efflux pumps.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Chenopodium ambrosioides/química , Monoterpenos/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Óleos Voláteis/farmacologia , Monoterpenos Cicloexânicos , Farmacorresistência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Norfloxacino/farmacologia , Óleos Voláteis/química , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismoRESUMO
Due to the great biodiversity of its flora, Brazil provides combat tools against bacterial resistance with the utilization of natural products with vegetable origin. Therefore, the present study had as its objective to evaluate the antibacterial potential of the Eugenia uniflora essential oil (EuEO) in vitro, as well as to analyze the modulatory effect of the oil against antibiotics by gaseous contact and to compare them when associated with a LED apparatus. The chemical components were characterised by gas chromatography which revealed the presence of the isoflurane-germacrene, considered the major component (61.69%). The MIC obtained from the EuEO was ≥256 µg/mL for S. aureus and ≥1024 µg/mL for E. coli. When combined with antibiotics, the EuEO presented synergism reducing the MIC when associated, with the exception of gentamicin against E. coli, where an antagonistic effect was observed. The was an interference of the EuEO over the activity of ciprofloxacin when associated with red and blue LED lights, increasing the inhibition halos against S. aureus and E. coli. Norfloxacin presented similar results to ciprofloxacin against S. aureus bacteria. When combined, norfloxacin and the EuEO presented synergism against S. aureus, which did not occur in the combination with ciprofloxacin. Interference occurred only with blue light for E. coli. Thus, it was observed that the EuEO causes changes in the activity of antibiotics, the same occurring with the use of LED lights, without significant differences in the association of the oil and the lights with the antibiotics tested. Further research is needed to elucidate the modulatory effects of the EuEO, as well as its association with LED lights.
Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Eugenia/química , Luz , Óleos Voláteis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Brasil , Cromatografia Gasosa , Ciprofloxacina/farmacologia , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Norfloxacino/farmacologia , Óleos Voláteis/isolamento & purificaçãoRESUMO
Bacterial resistance has risen as an important health problem with impact on the pharmaceutical industry because many antibiotics have become ineffective, which has affected their commercialization. The Brazilian biodiversity is marked by a vast variety of natural products with significant therapeutic potential, which could bring new perspectives in the treatment of infections caused by resistant microorganisms. The present study aimed to evaluate the antibacterial effect of the essential oil obtained from Eugenia jambolana (EjEO) using the method of microdilution method to determine the Minimum Inhibitory Concentration (MIC). The modulatory effect of this oil on antibiotic activity was determined using both the broth microdilution and gaseous contact methods. The antibacterial effect of the association of the gaseous contact and the use of a LED unit with red and blue lights was also determined. The chemical components of the EjEO were characterized by HPLC, which revealed the presence of α-pinene as a major constituent. The EjEO presented a MIC≥128µg/mL against S. aureus and ≥1024µg/mL against E. coli. The combination of the EjEO with antibiotics presented synergism against E. coli and antagonism against S. aureus. An antagonistic effect was obtained from the association of EjEO with amikacin and erythromycin by the method of gaseous contact. On the other hand, the association of EjEO with ciprofloxacin presented a synergistic effect against S. aureus and E. coli exposed to LED lights. A similar effect was observed in the association of the EjEO with norfloxacin presented synergism against S. aureus in the same conditions. In conclusion, our results demonstrated that the essential oil obtained from Eugenia jambolana interfere with the action of antibiotics against bacteria exposed to LED lights. Thus, further researches are required to elucidate the mechanisms underlying these effects, which could open new perspectives in the development of new antibacterial therapies.
Assuntos
Antibacterianos/farmacologia , Luz , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Syzygium/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiaçãoRESUMO
The use of natural products is crucial to suppress the development of these micro-organisms and to reduce the concentration necessary to inhibit these microrganisms, reducing the toxicity risks also. In this study, the essential oil from Chenopodium ambrosioides Leaves and its main constituent α-Terpinene were used in the antibacterial and potentiating activity of antibiotics and ethidium bromide assays, against the bacterial strains Staphylococcus aureus IS-58, carriers of efflux pumps. The Minimum Inhibitory Concentration (MIC) was determined using a microdilution method. The capacity of the aforementioned was also tested in combination with tetracycline and ethidium bromide, with the aim of improving the activity of the antibacterials. The MIC of the C. ambrosioides L. essential oil and of α-Terpinene were above 1024 µg/mL, comprising a clinically irrelevant value. However, when associated with the antibiotics, the C. ambrosioides L. essential oil, significantly decreased the MIC of tetracycline and ethidium bromide. The efflux pump is the only mechanism the bacteria possesses to reduce the toxicity of ethidium bromide, and thus this reduction in the MIC demonstrates that the C. ambrosioides L. essential oil is an effective option in the inhibition of the efflux pump present in these micro-organisms.