RESUMEN
This study continues the series of experiments that demonstrate the high antibacterial properties of monovalent copper ions (Cu+). While in previous study we examined different metals (copper and silver) and their metal states (mono- and divalent), showing that monovalent copper is best for controlling bacterial growth, the current study focuses on finding conditions which further enhance the antibacterial effect of monovalent copper. This approach may also shed light on mechanisms of Cu+ ions which still remain unknown. To this end, the influence of Cu+ ions on model gram-negative Escherichia coli bacteria at different pH levels with a variety of carbon sources and elevated temperatures was examined. It was found that in both aerobic and anaerobic conditions in a poor growth medium, Cu2+ ions barely suppress any growth of E. coli, whereas Cu+ ions even at very low concentrations dramatically deplete bacterial populations in a time scale of minutes at room temperature, and less than one minute at elevated temperatures. Acidic pH, unfavorable carbon sources, and elevated temperatures boost the antibacterial action of Cu+ ions. On the whole, the study confirms that monovalent copper ions are strongly superior to divalent copper ions in their antibacterial action across a wide range of tested conditions.
Asunto(s)
Antibacterianos/farmacología , Cobre/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Iones , Carbono/química , Medios de Cultivo/química , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , TemperaturaRESUMEN
This study opens the investigation series focused on antimicrobial effects of copper (Cu) compared to silver (Ag), which is currently used to treat wound infection in burn victims as well as in chronic wounds. Noticeably, in its ionized state, Cu is more commonly present as Cu2+ rather than as Cu+, while electronic configuration similarity of Cu+ and Ag+ indicates that actually it may be the active state. To test this hypothesis, effect of Cu+ and Cu2+, using Ag+ ions and metallic copper as controls on Escherichia coli and Staphylococcus aureus bacteria, was examined under anaerobic conditions. Cu+ was produced by two different methods, and its effect on microorganism growth was tested using a syringe and Petri dish methods. It was found that the presence of Cu+ causes a dramatic depletion in the viability of both microorganisms. Metallic copper did not have any effect on the viability, whereas Cu2+ and Ag+ ions had much lower activity than Cu+ ions. Minimal inhibitory concentration of Cu+ for E. coli was twice lower than that of Cu2+. The obtained results show that Cu+ proves to be a potent antimicrobial agent.
Asunto(s)
Antiinfecciosos/farmacología , Cobre/farmacología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antiinfecciosos/química , Cobre/química , Escherichia coli/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Plata/farmacología , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
Ferritin has gained significant attention as a potential reporter gene for in vivo imaging by magnetic resonance imaging (MRI). However, due to the ferritin ferrihydrite core, the relaxivity and sensitivity for detection of native ferritin is relatively low. We report here on a novel chimeric magneto-ferritin reporter gene - ferritin-M6A - in which the magnetite binding peptide from the magnetotactic bacteria magnetosome-associated Mms6 protein was fused to the C-terminal of murine h-ferritin. Biophysical experiments showed that purified ferritin-M6A assembled into a stable protein cage with the M6A protruding into the cage core, enabling magnetite biomineralisation. Ferritin-M6A-expressing C6-glioma cells showed enhanced (per iron) r2 relaxivity. MRI in vivo studies of ferritin-M6A-expressing tumour xenografts showed enhanced R2 relaxation rate in the central hypoxic region of the tumours. Such enhanced relaxivity would increase the sensitivity of ferritin as a reporter gene for non-invasive in vivo MRI-monitoring of cell delivery and differentiation in cellular or gene-based therapies.