Thiazine-derived compounds in inhibiting efflux pump in Staphylococcus aureus K2068, mepA gene expression, and membrane permeability alteration.

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.

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study's objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains.

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure-activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.

Cytotoxicity of Essential Oil Cordia verbenaceae against Leishmania brasiliensis and Trypanosoma cruzi.

The species Cordia verbenacea DC (Boraginaceae), known as the whaling herb and camaradinha, is a perennial shrub species native to the Atlantic Forest. Its leaves are used in folk medicine as an anti-inflammatory, analgesic, antiulcerogenic and curative agent, in the form of teas or infusions for internal or topical use. The present study aimed to verify the cytotoxicity of the essential oil and the leishmanicidal and trypanocidal potential of C. verbenacea. The essential oil was characterized by GC-MS. The in vitro biological activity was determined by anti-Leishmania and anti-Trypanosoma assays. The cytotoxixity was determined using mammalian fibroblasts. The C. verbenacea species presented α-pinene (45.71%), ß-caryophyllene (18.77%), tricyclo[2,2,1-(2.6)]heptane (12.56%) as their main compounds. The essential oil exhibited strong cytotoxicity at concentrations below 250 µg/mL (LC50 138.1 µg/mL) in mammalian fibroblasts. The potent anti-trypanosome and anti-promastigote activities occurred from the concentration of 62.5 µg/mL and was considered clinically relevant. The results also demonstrate that at low concentrations (<62.5 µg/mL), the essential oil of C. verbenacea managed to be lethal for these activities. This can be considered an indication of the power used in daily human consumption. Therefore, it can be concluded that the essential oil of C. verbenacea contains a compound with remarkable antiparasitic activities and requires further research.

Enhancement of the antibiotic activity by quercetin against Staphylococcus aureus efflux pumps.

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.

Modulation of Drug Resistance by Limonene: Inhibition of Efflux Pumps in Staphylococcus aureus Strains RN-4220 and IS-58.

AIMS: This study aimed to investigate the potential of limonene as an efflux pump (EP) inhibitor in Staphylococcus aureus strains, RN-4220 and IS-58, which carry EPs for erythromycin (MrsA) and tetracycline (TetK), respectively. BACKGROUND: The evolution of bacterial resistance mechanisms over time has impaired the action of most classes of antibiotics. Staphylococcus aureus is a notable bacterium, with high pathogenic potential and demonstrated resistance to conventional antibiotics. Considering the importance of discovering novel compounds to combat antibiotic resistance, our group previously demonstrated the antibacterial properties of limonene, a compound present in the essential oils of several plant species. OBJECTIVE: This study aimed to investigate the potential of limonene as an efflux pump (EP) inhibitor in Staphylococcus aureus strains RN-4220 and IS-58, which carry EPs for erythromycin (MrsA) and tetracycline (TetK), respectively. METHODS: The minimum inhibitory concentrations (MIC) of limonene and other efflux pump inhibitors were determined through the broth microdilution method. A reduction in the MIC of ethidium bromide was used as a parameter of EP inhibition. RESULT: While limonene was not shown to exhibit direct antibacterial effects against EP-carrying strains, in association with ethidium bromide and antibiotics, this compound demonstrated enhanced antibacterial activity, indicating the inhibition of the MrsA and TetK pumps. CONCLUSION: In conclusion, this pioneering study demonstrated the effectiveness of limonene as an EP inhibitor in S. aureus strains, RN-4220 and IS-58. Nevertheless, further studies are required to characterize the molecular mechanisms associated with limonene-mediated EP inhibition.

Inhibition of Efflux Pumps by Monoterpene (α-pinene) and Impact on Staphylococcus aureus Resistance to Tetracycline and Erythromycin.

INTRODUCTION: Infectious diseases have been responsible for an increasing number of deaths worldwide. Staphylococcus aureus has been recognized as one of the most notable causative agents of severe infections, while efflux pump (EP) expression is one of the main mechanisms associated with S. aureus resistance to antibiotics. OBJECTIVE: This study aimed to investigate the potential of &#945;-pinene as an efflux pump inhibitor in species of S. aureus carrying the TetK and MrsA proteins. METHODS: The minimum inhibitory concentrations (MIC) of &#945;-pinene and other efflux pump inhibitors were assessed using serial dilutions of each compound at an initial concentration above 1024 µg/mL. Solutions containing culture medium and bacterial inoculums were prepared in test tubes and subsequently transferred to 96-well microdilution plates. The modulation of ethidium bromide (EtBr) and antibiotics (tetracycline and erythromycin) was investigated through analysis of the modification in their MICs in the presence of a subinhibitory concentration of &#945;-pinene (MIC/8). Wells containing only culture medium and bacterial inoculums were used as negative control. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) was used as a positive control. RESULTS: The MIC of ethidium bromide against S. aureus strains RN-4220 and IS-58 was reduced by association with α-pinene. This monoterpene potentiated the effect of tetracycline against the IS-58 strain but failed in modulating the antibacterial effect of erythromycin against RN-4220, suggesting a selective inhibitory effect on the TetK EP by &#945;- pinene. CONCLUSION: In conclusion, α-pinene has promising effects against S.aureus strains, which should be useful in the combat of antibacterial resistance associated with EP expression. Nevertheless, further research is required to fully characterize its molecular mechanism of action as an EP inhibitor.

Potentiation of antibiotic activity by chalcone (E)-1-(4'-aminophenyl)-3-(furan-2-yl)-prop-2-en-1-one against gram-positive and gram-negative MDR strains.

Chalcones are α,ß-unsaturated ketones containing the 1,3-diarylprop-2-en-1-one framework. This study aims to evaluate the potentiation of antibacterial activity by the chalcone (E)-1-(4-aminophenyl)-3-(furan-2-yl)-prop-2-en-1-one (C13H11NO2), hereafter named AFPO, against multi-resistant strains of Staphylococcus aureus and Escherichia coli. AFPO was synthesized using the Claisen-Schmidt condensation reaction, and the molecular structure was confirmed by nuclear magnetic resonance (NMR). The antibacterial and potentiating properties of AFPO were evaluated by measuring the minimum inhibitory concentration (MIC) using microdilution plates. The AFPO MIC was 1024 µg/mL for the S. aureus 10 strain, revealing synergy in combination with the following antibiotics: penicillin, norfloxacin, ampicillin/sulbactam, and gentamicin. The AFPO MIC was 256 µg/mL for the E. coli 06 strain, and synergy was observed with norfloxacin, gentamicin, and penicillin. The potentiation of antibacterial activity by AFPO was observed against the strains of S. aureus 10 and E. coli 06.

Effect of Vitamin K3 Inhibiting the Function of NorA Efflux Pump and Its Gene Expression on Staphylococcus aureus.

Resistance to antibiotics has made diseases that previously healed easily become more difficult to treat. Staphylococcus aureus is an important cause of hospital-acquired infections and multi-drug resistant. NorA efflux pump, present in bacteria S. aureus, is synthesized by the expression of the norA gene. Menadione, also known as vitamin K3, is one of the synthetic forms of vitamin K. Therefore, the aim of this study is to verify the menadione effect on efflux inhibition through NorA pump gene expression inhibition and assess the effects of menadione in bacterial membrane. The effect of menadione as an efflux pump inhibitor (EPI) was evaluated by the microdilution method, fluorimetry, electron microscopy, and by RT-qPCR to evaluate gene expression. In the molecular docking, association with menadione induces increased fluorescence intensity. Menadione was observed (100% of the clusters) interacting with residues ILE12, ILE15, PHE16, ILE19, PHE47, GLN51, ALA105, and MET109 from NorA. The results showed the norA gene had its expression significantly diminished in the presence of menadione. The simulation showed that several menadione molecules were able to go through the bilayer and allow the entry of water molecules into the hydrophobic regions of the bilayer. When present within membranes, menadione may have caused membrane structural changes resulting in a decline of the signaling pathways involved in norA expression. Menadione demonstrated to be an efflux pump inhibitor with dual mechanism: affecting the efflux pump by direct interaction with protein NorA and indirectly inhibiting the norA gene expression, possibly by affecting regulators present in the membrane altered by menadione.

GC-MS Profile and Enhancement of Antibiotic Activity by the Essential Oil of Ocotea odorífera and Safrole: Inhibition of Staphylococcus aureus Efflux Pumps.

Considering the evidence that essential oils, as well as safrole, could modulate bacterial growth in different resistant strains, this study aims to characterize the phytochemical profile and evaluate the antibacterial and antibiotic-modulating properties of the essential oil Ocotea odorífera (EOOO) and safrole against efflux pump (EP)-carrying strains. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). The antibacterial and antibiotic-modulating activities of the EOOO and safrole against resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were analyzed through the broth microdilution method. The EP-inhibiting potential of safrole in association with ethidium bromide or antibiotics was evaluated using the S. aureus 1199B and K2068 strains, which carry genes encoding efflux proteins associated with antibiotic resistance to norfloxacin and ciprofloxacin, respectively. A reduction in the MIC of ethidium bromide or antibiotics was used as a parameter of EP inhibition. The phytochemical analysis identified 16 different compounds in the EOOO including safrole as the principal constituent. While the EOOO and safrole exerted clinically relevant antibacterial effects against S. aureus only, they potentiated the antibacterial activity of norfloxacin against all strains evaluated by our study. The ethidium bromide and antibiotic assays using the strains of S. aureus SA1119B and K2068, as well as molecular docking analysis, indicated that safrole inhibits the NorA and MepA efflux pumps in S. aureus. In conclusion, Ocotea odorifera and safrole presented promising antibacterial and antibiotic-enhancing properties, which should be explored in the development of drugs to combat antibacterial resistance, especially in strains bearing genes encoding efflux proteins.

Evaluation of antibacterial and enhancement of antibiotic action by the flavonoid kaempferol 7-O-ß-D-(6″-O-cumaroyl)-glucopyranoside isolated from Croton piauhiensis müll.

There has been a rapid increase in the incidence and prevalence of opportunistic bacterial infections. Inappropriate use of current antibiotics has continuously contributed to the emergence of resistance to conventional antibiotic therapy. Therefore, the search for natural molecules that are able to combat infections is of great public interest, and many of these compounds with antimicrobial properties can be obtained from phytochemical studies of medicinal plants. In this context, this study reports the isolation and characterization of the flavonoid, kaempferol 7-O-ß-D-(6″-O-cumaroyl)-glucopyranoside, from Croton piauhiensis leaves. Additionally, the intrinsic antimicrobial action of the compound and its enhancement against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains were assessed. The minimum inhibitory concentration (MIC) of the compound was determined using broth microdilution assays. To evaluate the modulatory effect of the flavonoid, the MIC of antibiotics amikacin and gentamicin, belonging to the class aminoglycosides was assessed, with and without the compound in sterile microplates. The results of intrinsic antibacterial activity tests revealed that the compound had no antibacterial activity against strains tested at concentrations <1024 µg/mL. The combination of the flavonoid at a concentration of 128 µg/mL with gentamicin presented synergistic effects against S. aureus 10 and E. coli 06, and also reduced the MIC from 16 µg/mL to 4 µg/mL and 8 µg/mL, respectively. Amikacin also showed synergistic effects against S. aureus 10 and E. coli 06. We also observed reduced MIC for both, from 128 µg/mL to 32 µg/mL; however, antagonism for P. aeruginosa increased the MIC from 16 µg/mL to 64 µg/mL. The combination of the flavonoid with the aminoglycosides may be an alternative to potentiate the expected results in treatment against S. aureus and E. coli, since their association leads to a synergistic effect, reducing the MIC of these drugs and decreasing the dose necessary for therapeutic success.

Essential Oil of Croton ceanothifolius Baill. Potentiates the Effect of Antibiotics against Multiresistant Bacteria.

This study is a pioneer in reporting the antibacterial properties of the species Croton ceanothifolius Baill. The genus Croton belongs to the family Euphorbiaceae composed of numerous species with documented biological activities. However, the pharmacological properties of C. ceanothifolius remain poorly understood. The leaves of this plant were submitted to hydrodistillation for essential oil (CcEO) extraction and the phytochemical characterization of the oil was performed by GC/MS. The minimum inhibitory concentration of the CcEO was determined for the evaluation of antibacterial activity against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The antibiotic-modulating activity of the oil, in combination with antibiotics, was also evaluated. The combination of the CcEO with penicillin, norfloxacin, and gentamicin presented a synergistic effect. This effect was more significant for the association with antibiotics of the quinolone and aminoglycoside classes against Escherichia coli. The association of oil with gentamicin showed better results with regard to the Gram-positive strain. The association of the oil with norfloxacin against P. aeruginosa also showed synergism, but the association with penicillin did not change the effect of this antibiotic. Thus, it is concluded that C. ceanothifolius essential oil selectively potentiates the action of antibiotics against multiresistant strains.

Characterization, antibacterial activity and antibiotic modifying action of the Caryocar coriaceum Wittm. pulp and almond fixed oil.

In this study the physicochemical characterization of the pulp and almond fixed oil was carried out; their antibacterial activity and aminoglycoside antibiotic modifying action against standard and multiresistant Gram-positive and -negative bacteria were investigated using the broth microdilution assay. Physical properties such as moisture, pH, acidity, peroxide index, relative density and refractive index indicate stability and chemical quality of the oils. In the GC/MS chemical composition analysis, a high unsaturated fatty acid content and the presence of oleic and palmitic acids were observed in the oils. In the antibacterial assay, more significant results were obtained for Escherichia coli, while other standard and multi-resistant strains presented MIC values ≥ 1024 µg/mL. Furthermore, the fixed oils in association with antibiotics were able to significantly improve antibacterial activity against S. aureus with a reduction in MICs.

Potentiation of antibiotic activity by Passiflora cincinnata Mast. front of strains Staphylococcus aureus and Escherichia coli.

The development of new drugs from plants is an interesting alternative approach to overcoming microbial resistance. Passiflora cincinnata shows resistance to diseases and pests and a higher concentration of chemical components that may be useful in the pharmaceutical industry. We investigated the potential antimicrobial and antibiotic-modifying activity of hydroalcoholic extracts of leaves, stems, bark, pulp and seeds of P. cincinnata. The extracts were prepared by homogenization of material in 50% ethanol. Minimum inhibitory concentration (MIC) was determined by the broth dilution method, and the bacterial strains tested were Staphylococcus aureus and Escherichia coli. Antibiotic-modifying activity was evaluated against the strains S. aureus 03 and E. coli 08, using a subinhibitory concentration of extract. The antibiotics tested were: amikacin, gentamicin, ampicillin, potassium benzylpenicillin and oxacillin. The extracts did not show antimicrobial activity of clinical relevance, where the MIC was equal to or greater than 1024 µg/mL. S. aureus showed 13 events, while E. coli showed only 4 events. Among these events, 14 involved synergistic activity, potentiating the effect of the antibiotics, and only 3 events demonstrated antagonistic activity toward ampicillin. Hydroalcoholic extracts are potential antimicrobial agents when combined with conventional drugs little utilized in in vivo treatment.

Cholecalciferol, Ergosterol, and Cholesterol Enhance the Antibiotic Activity of Drugs.

Background: This is the first report demonstrating the antibiotic-modifying activity of cholecalciferol. AIM: In this study, cholecalciferol was evaluated against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. METHODS: The antibacterial and modulatory effects of cholecalciferol, ergosterol, and cholesterol (8-512 µg/mL) were evaluated by microdilution assay against multiresistant bacterial strains. RESULTS: Cholecalciferol, when combined with aminoglycosides, was more effective against P. aeruginosa, reducing the concentration of amikacin and gentamicin necessary to inhibit bacterial growth from 156.25 to 39.06 µg/mL and from 39.06 to 9.76 µg/mL, respectively. It is possible that cholecalciferol, due to its lipid-soluble nature, had a lipophilic interaction with the cell membrane, enhancing antibiotic uptake. Cholesterol and ergosterol were used to see if the mechanism of action of cholecalciferol was similar to that of these lipid compounds. Ergosterol and cholesterol increased aminoglycoside activity, where the effect was greater with higher subinhibitory concentration of sterol. CONCLUSIONS: There is no reported study on the use of cholesterol and ergosterol as modulators of antibiotics or any other drug, making this the first study in this area highlighting the interaction between cholesterol, ergosterol, and cholecalciferol with regard to modifying aminoglycoside activity.

Tannic acid affects the phenotype of Staphylococcus aureus resistant to tetracycline and erythromycin by inhibition of efflux pumps.

The widespread use of antibiotics created selective pressure for the emergence of strains that would persist despite antibiotic toxicity. The bacterial resistance mechanisms are several, with efflux pumps being one of the main ones. These pumps are membrane proteins with the function of removing antibiotics from the cell cytoplasm. Due to this importance, the aim of this work was to evaluate the inhibitory effect of tannic acid against efflux pumps expressed by the Staphylococcus aureus RN4220 and IS-58 strains. The efflux pump inhibition was assayed using a sub-inhibitory concentration of efflux pump standard inhibitors and tannic acid (MIC/8), observing their capacity to decrease the MIC of Ethidium bromide (EtBr) and antibiotics due the possible inhibitory effect of these substances. The MICs of EtBr and antibiotics were significantly different in the presence of tannic acid, indicating the inhibitory effect of this product against efflux pumps of both strains. These results indicate the possible usage of tannic acid asan inhibitor and an adjuvant in the antibiotic therapy against multidrug resistant bacteria (MDR).

Inhibition of the TetK efflux-pump by the essential oil of Chenopodium ambrosioides L. and α-terpinene against Staphylococcus aureus IS-58.

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.

Menadione (vitamin K) enhances the antibiotic activity of drugs by cell membrane permeabilization mechanism.

Menadione, vitamin K3, belongs to the class of lipid-soluble vitamins and lipophilic substances as menadione cause disturbances in the bacterial membrane, resulting in damage to the fundamental elements for the integrity of the membrane, thus allowing increased permeability. Accordingly, the aim of this study was to evaluate in vitro the antibiotic-modifying activity of menadione in multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, with a gradual increase in its subinhibitory concentration. In addition, menadione was compared with cholesterol and ergosterol for similarity in mechanism of drug modulatory action. Antibiotic-modifying activity and antibacterial effect were determined by the broth microdilution assay. Menadione, cholesterol and ergosterol showed modulatory activity at clinically relevant concentrations, characterizing them as modifiers of bacterial drug resistance, since they lowered the MIC of the antibiotics tested. This is the first report of the antibacterial activity of menadione and its potentiation of aminoglycosides against multiresistant bacteria.

Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol.

The indiscriminate use of antimicrobial drugs has increased the spectrum of exposure of these organisms. In our studies, these phenolic compounds were evaluated: gallic acid, caffeic acid and pyrogallol. The antibacterial, antifungal and modulatory of antibiotic activities of these compounds were assayed using microdilution method of Minimum Inhibitory Concentration (MIC) to bacteria and Minimum Fungicide Concentration (MFC) to fungi. The modulation was made by comparisons of the MIC and MFC of the compounds alone and combined with drugs against bacteria and fungi respectively, using a sub-inhibitory concentration of 128 µg/mL of substances (MIC/8). All substances not demonstrated clinically relevant antibacterial activity with a MIC above ≥1024 µg/mL. As a result, we observed that the caffeic acid presented a potentiating antibacterial effect over the 3 groups of bacteria studied. Pyrogallol showed a synergistic effect with two of the antibiotics tested, but only against Staphylococcus aureus. In general, caffeic acid was the substance that presented with the greatest number of antibiotics and with the greatest number of bacteria. In relation to the antifungal activity of all the compounds, the verified results were ≥1024 µg/mL, not demonstrating significant activity. Regarding potentiation of the effect of fluconazole, was observed synergistic effect only when assayed against Candida tropicalis, with all substances. Therefore, as can be seen, the compounds presented as substances that can be promising potentiating agents of antimicrobial drugs, even though they do not have direct antibacterial and antifungal action.

Avaliação da atividade antibacteriana dos extratos metanólico e hexânico do caule folhado de Melissa Officinalis / Evaluation of the Antibacterial Activity of Methanolic and Hexanic Extracts of Puff Pastry Stem, Melissa Officinalis / Evaluación de la actividad antibacterial de extractos metanol y hexano, el tallo rodadura Melissa Officinalis

Introdução: Melissa officinalis, da família Lamiaceae, é uma erva comumente utilizada na medicina popular. É conhecida no Brasil como Melissa, erva cidreira, cidrilha e melitéia. Tendo em vista que M.officinalis L é largamente utilizada na medicina popular, dentre elas para uso antibacteriano, este trabalho teve como principal objetivo avaliar a atividade antibacteriana e modulatória de extratos metanólico e hexânico do caule folhado de M. officinalis frente a cepas de bactérias padrões e multirresistentes. Materiais e métodos: Os extratosmetanólico e hexânico do caule folhado de M. officinalis L foram analisados para a atividade antibacteriana por meio de teste de microdiluição para determinação de concentração inibitória mínima (CIM) e modulação de aminoglicosídeos (gentamicina e amicacina). Resultados: Na avaliação DACIM foram obtidos resultados ≥1024 μg/mLcontra as bactérias (Escherichia coli e Staphylococcus aureus) em ambos extratos. O extrato metanólico mostrou resultados relevantes em associação com gentamicina potencializando o efeito contra E. coli e S. aureus quando associado à amicacina, nesta bactéria houve antagonismo. Já o extrato hexânico, resultou em uma redução da CIM de amicacina e gentamicina frente a linhagens de E. coli, mostrando efeito antagonista com a amicacina conta cepas de S. aureus. Conclusão: Conclui-se que o material vegetal influencia no comportamento dos antimicrobianos, tornando este trabalho importante como parâmetro para estudos mais aprofundados que possam combater a crescente resistência de bactérias patogênicas.

Introduction: Melissa officinalis, of the Lamiaceae family, is a herb commonly used on folk medicine. In Brazil it is known as Melissa, erva cidreira, cidrilha and meliteia. Considering that the M. Officinalis L is widely used in folk medicine, as for antibacterial use, among others, the main objective of this work was to evaluate the antibacterial and modulating activity of methanolic and hexanic extracts of M. officinalis L against pattern and multidrug resistant bacterial strains. Material and methods: The methanolic and hexanic extracts of the stem of puff pastry of M. officinalis L were analized to determine antibacterial activity by using the microdiluition for establishing the minimal inibitory concentration (MIC) and aminoglycosides (gentamicin and amikacin) modulation. Results: In the MIC evaluation, the results obtained were ≥1024 μg/mL against bacteria (Escherichia coli and Staphylococcus aureus) in both extracts. The methanolic extract showed important results when associated with gentamicin, since it potentiates its effect against E. coli and S. aureus when associated with amikacin, where antagonism was found. As to the hexanic extract, it showed a MIC reduction of amikacin and gentamicin against S. aureus strains. Conclusion: It was concluded that the plant material influences the antimicrobial behavior, a fact that makes this study an important parameter to deeper studies to combat the increase of pathogenic multidrug-resistant bacteria.

Introducción: Melissa Officinalis, de la familia Lamiaceae, es una hierba utilizada en la medicina popular. Es conocido en Brasil como erva cidreira, melisa, y melitéia cidrilha. Teniendo en cuenta que M. Officinalis L. se utiliza ampliamente en la medicina popular, entre ellos para uso antibacteriano, este trabajo tuvo como objetivo evaluar la actividad antibacteriana y modulador de extracto de metanol y hexano rodar el tallo de M. officinalis L. frente a las cepas de bacterias normas y las bacterias multirresistentes. Materiales y métodos: se analizó el extracto de metanol y hexano del tallo rodadura M. Officinalis L. para la actividad antibacteriana por una prueba de microdilución para la determinación de la Concentración Mínima Inhibitoria (MIC) y la modulación de aminoglucósidos (gentamicina y amikacina). Resultados: en la evaluación de la MIC los resultados obtenidos fueron ≥1024 μg/ml con contra las bacterias (Escherichia coli y Staphylococcus aureus) en ambos extractos. El extracto de metanol mostró resultados significativos en combinación con efecto potenciador gentamicina contra E. coli y s. Aureus cuando se combina con amikacina, esta bacteria era antagonismo. Ya extracto de hexano dio lugar a una reducción de la MIC de amikacina y gentamicina contra cepas de E. coli, que muestra el efecto antagónico con cepas de la cuenta de amikacina de S. Aureus. Conclusión: se concluye que el material vegetal influye en el comportamiento de los antimicrobianos, lo que hace este trabajo importante como parámetro para futuros estudios que puedan combatir la creciente resistencia de las bacterias.