Efflux Pump (QacA, QacB, and QacC) and ß-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains.

The bacterial species Staphylococcus aureus presents a variety of resistance mechanisms, among which the expression of ß-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of ß-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of S. aureus. All substances were prepared at an initial concentration of 1024 µg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on ß-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and ß-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of S. aureus. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and ß-lactam antibiotics, suggesting that they may act by inhibiting ß-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects.

Silver Trimolybdate (Ag2Mo3O10.2H2O) Nanorods: Synthesis, Characterization, and Photo-Induced Antibacterial Activity under Visible-Light Irradiation.

The present study reports the synthesis, characterization, and antibacterial properties of silver trimolybdate (Ag2Mo3O10.2H2O) nanorods. The synthesis was performed using a conventional hydrothermal method. The sample was characterised by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, UV-Vis-NIR diffuse reflectance, thermogravimetric analysis (TGA), and differential scanning calorimeter (DSC). The direct antibacterial activity was evaluated using the microdilution method to determine the minimum inhibitory concentration (MIC). To assess the ability of Ag2Mo3O10.2H2O nanorods to modulate antibacterial resistance, the MIC of aminoglycosides was established in the presence of a subinhibitory concentration of this substance alone and associated with LED light exposure. The characterization of the sample indicated that the synthesis of silver trimolybdate generated nanometric crystals with rod-like morphology, without secondary phases. The treatment with Ag2Mo3O10.2H2O nanorods alone or combined with visible LED lights exhibited clinically relevant antibacterial activity against both Gram-negative and Gram-positive bacteria. This nanostructure presented a variable antibiotic-modulating action, which was not improved by visible LED light exposure. Nevertheless, LED lights showed promising antibiotic-enhancing activities in the absence of Ag2Mo3O10.2H2O nanorods. In conclusion, silver trimolybdate dihydrate nanorods have antibacterial properties that can be photocatalysed by visible-light exposure. While showing the potential use to combat antibacterial resistance, the simultaneous combination of silver trimolybdate, visible LED lights, and antibacterial drugs should be carefully analysed to avoid antagonist effects that could impair the effectiveness of antibiotic therapy.

Liposome evaluation in inhibiting pump efflux of NorA of Staphylococcus aureus.

Liposomes, in addition to providing greater efficacy to antibiotics, decrease toxicity and increase selectivity. This work has as main objectives the sensitization of the need to solve bacterial resistance to antibiotics, addressing the potential of antibiotics carried by liposome. In the preparation of the liposomes, the lipids dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylserine (DPPS), and cholesterol (COL) with > 99% purity were used. The Staphylococcus aureus strains used were SA-1199B, which expresses the NorA gene encoding the NorA efflux protein, which expels hydrophilic fluoroquinolones and other drugs intercalating DNA dyes, and the wild strain SA-1199. The liposomes associated with antibiotics in the wild type of strain SA-1199 and the carrier strain of pump 1199B, had a better representation of growth inhibition than the wild type strain SA-1199. Given the potential for inhibition of efflux pump seen in the results, we highlight the creation of new drugs or alteration of existing drugs. They are not recognized by the efflux pumps and removed from the target cell.

GC-MS-FID characterization and antibacterial activity of the Mikania cordifolia essential oil and limonene against MDR strains.

The present study evaluated the effect of the essential oil of Mikania cordifolia (EOMc) and its major constituent limonene alone or associated with antibacterial drugs against Multidrug Resistant Bacteria (MDR). To evaluate the antibacterial activity, the minimum inhibitory concentrations (MIC) of the oil and limonene against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus were determined. The antibiotic-modulating activity was assessed using subinhibitory concentrations (MIC/8) of these substances in combination with conventional antibacterial drugs. Although no relevant antibacterial activity of the natural products was detected, both substances modulated the action of antibiotics against resistant bacteria. The EOMc demonstrated the best modulating effect against P. aeruginosa, presenting synergistic effects when associated with gentamicin and norfloxacin. In addition, the oil reduced the MIC of norfloxacin against E. coli as well as reduced the MIC of gentamicin against S. aureus. On the other hand, the best effect of limonene was obtained against S. aureus. Thus, it is concluded that the essential oil Mikania cordifolia and the isolated compound limonene do not have clinically significant antibacterial effect, but modulate the action of antibiotics against MDR bacteria.

Photoinduced Antibacterial Activity of the Essential Oils from Eugenia brasiliensis Lam and Piper mosenii C. DC. by Blue Led Light.

The objective of this work was to evaluate the phytochemical composition and the antibacterial and antibiotic-modulating activities of the essential oils of Eugenia brasiliensis Lam (OEEb) and Piper mosenii C. DC (OEPm) singly or in association with blue LED (Light-emitting diode) light. The antibacterial and antibiotic-modulatory activities of the essential oils on the activity of aminoglycosides were evaluated to determine the minimum inhibitory concentration (MIC, µg/mL) in the presence or absence of exposure to blue LED light. The chemical analysis showed α-pinene and bicyclogermacrene as major constituents of OEPm, whereas α-muurolol was the main compound of OEEb. Both OEEb and OEPm showed MIC ≥ 512 µg/mL against the strains under study. However, the association of these oils with the blue LED light enhanced the action of the aminoglycosides amikacin and gentamicin. In conclusion, the association of aminoglycosides with the blue LED light and essential oils was effective against resistant bacteria.