RESUMO

The increasing antifungal resistance rates against conventional drugs reveal the urgent need to search for new therapeutic alternatives. In this context, natural bioactive compounds have a critical role in antifungal drug development. Since evidence demonstrates that abietic acid, a diterpene found in Pinus species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against Candida spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against Candida albicans (CA INCQS 40006), Candida krusei (CK INCQS 40095), and Candida tropicalis (CT INCQS 40042). The microdilution method was used to determine the IC50 and the cell viability curve. Minimum Fungicidal Concentration (MFC) was determined by subculture in a solid medium. The plasma membrane permeability was measured using a fluorescent SYTOX Green probe. While the IC50 of the drugs alone ranged between 1065 and 3255 µg/mL, the IC50 resulting from the combination of abietic acid and fluconazole ranged between 7563 and 160.1 µg/mL. Whether used in combination with fluconazole or isolated, abietic acid exhibited Minimum Fungicidal Concentration (MFC) values exceeding 1024 µg/mL against Candida albicans, Candida krusei and Candida tropicalis. However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against Candida albicans and Candida tropicalis. These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance.

RESUMO

A worrisome fact is the increase in microbial resistance, which has as its main cause the indiscriminate use of antibiotics. Scientific studies have investigated bioactive compounds such as steroidal sapogenins, in the perspective of new beneficial alternatives for the control of bacterial resistance. Therefore, the objective of this work was to verify the antibacterial activity as well as the modifying action of antibiotics associated with solasodine and its ability to inhibit the efflux pump mechanism in strains of Staphylococcus aureus. Tests were performed to verify the minimum inhibitory concentration (MIC). In addition, the action-modifying potential of antibiotics and the inhibitory capacity of the efflux pump NorA and MepA through synergistic effects on the antibiotic and ethidium bromide were evaluated. Solasodine showed significant results for the standard bacteria with an MIC of 512 µg/mL, and when associated with the antibiotics gentamicin and nofloxacin for the multidrug-resistant bacteria S. aureus 10, Escherichia coli 06, and Pseudomonas aeruginosa 24, it showed a 50% reduction in MIC. The association of solasodine with the antibiotic ciprofloxacin against S. aureus K2068 (MepA) showed synergism, with a reduction in the MIC of the antibiotic from 64 µg/mL to 40 µg/mL, and also a reduction in the MIC when the antibiotic was used in conjunction with the efflux pump inhibitors. Solasodine may be acting on the mechanism of action of the antibiotic, as it has shown a potentiating effect when associated with antibiotics, inducing a reduction in the MIC against Gram-positive and Gram-negative bacteria. Therefore, this study demonstrated significant results for the potentiating action of solasodine when associated with antibiotics of clinical importance.

RESUMO

The number of arbovirus cases has increased in recent years, demonstrating a need for investing in effective control actions. Among these actions, are strategies using biological control vectors, a field where Wolbachia pipientis has shown itself as useful. Wolbachia pipientis, an obligatory intracellular Gram-negative bacteria, which parasites arthropods naturally or through laboratory-induced infections, is capable of manipulating the reproduction of its host. A systematic literature review gathering studies on this bacteria over last 10 years (2007-2021) was performed given its important role in the reduction of insect disease vectors. 111 articles were found, from which 78 were used in this study. Information on the Wolbachia biology, mechanism of action and potential for the biological control of insect disease vectors was gathered. The present study may contribute to the knowledge surrounding the bacterium, as well as stimulate the production of other studies with the same theme.

Assuntos

RESUMO

Lectins participate in the defense against microorganisms and in signaling the damage caused by pathogens to the cell surface and/or intracellular in plants. This study aims to analyze the antifungal potential of lectins extracted from seeds of Canavalia ensiformis (L.) DC and Canavalia rosea (Sw.) DC, against Candida albicans and Candida tropicalis. The antimicrobial tests were performed by microdilution against Candida spp. The test to verify the combined lectin/fluconazole effect was performed using subinhibitory concentrations of lectins and with antifungal ranging from 0.5 to 512 µg/mL. The ability to inhibit the morphological transition of Candida spp. was evaluated by microcultivation in a moist chamber. The results of the minimum inhibitory concentration revealed no antifungal activity against the tested strains. However, lectins modified the action of fluconazole, reducing the IC50 of the drug against C. albicans. Lectins were also able to discretely modulate the morphological transition of the tested strains.

Assuntos

RESUMO

Bacterial resistance is a natural process carried out by bacteria, which has been considered a public health problem in recent decades. This process can be triggered through the efflux mechanism, which has been extensively studied, mainly related to the use of natural products to inhibit this mechanism. To carry out the present study, the minimum inhibitory concentration (MIC) tests of the compound limonene were performed, through the microdilution methodology in sterile 96-well plates. Tests were also carried out with the association of the compound with ethidium bromide and ciprofloxacin, in addition to the ethidium bromide fluorimetry, and later the molecular docking. From the tests performed, it was possible to observe that the compound limonene presented significant results when associated with ethidium bromide and the antibiotic used. Through the fluorescence emission, it was observed that when associated with the compound limonene, a greater ethidium bromide fluorescence was emitted. Finally, when analyzing the in silico study, it demonstrated that limonene can efficiently fit into the MepA structure. In this way, it is possible to show that limonene can contribute to cases of bacterial resistance through an efflux pump, so that it is necessary to carry out more studies to prove its effects against bacteria carrying an efflux pump and assess the toxicity of the compound.

Assuntos

RESUMO

Since the discovery of the first antibiotics, bacteria have acquired a variety of resistance mechanisms, with efflux pump (EP) being the most prominent mechanism for intracellular targeting drugs. These proteins have become efficient mechanisms of resistance to antibiotics in species such as Staphylococcus aureus and, therefore, have been identified as promising therapeutic targets in antibacterial drug development. Accordingly, evidence suggests that monoterpenes can act as EP inhibitors and can be useful in circumventing bacterial resistance. This study aimed to evaluate the effectiveness of monoterpenes α-pinene and limonene as EP inhibitors against a strain of S. aureus expressing NorA protein. The minimum inhibitory concentration (MIC) against the 1199B strain of S. aureus, which carries genes encoding efflux proteins associated with antibiotic resistance to norfloxacin, was assessed through the broth microdilution method. The results obtained served as a subsidy for the analysis of the NorA pump inhibition with norfloxacin and ethidium bromide. Docking techniques, in silico, were used to evaluate the interaction of monoterpenes with NorA. Both monoterpenes showed no clinically effective antibacterial activity. Nevertheless, these compounds were found to decrease the MICs of ethidium bromide and norfloxacin indicating EP inhibition, which was confirmed by molecular docking analyses. In conclusion, α-pinene and limonene showed promising antibiotic-enhancing properties in S. aureus 1199B strain, indicating that monoterpenes can be used in targeted drug development to combat antibiotic resistance associated with EP expression.

Assuntos