ИСТИНА

Mitochondria-targeted antioxidants are known to alleviate mitochondrial oxidative damage that causes a variety of diseases. By monitoring time courses of optical density at 620 nm after 2-fold broth microdilution, we found that SkQ1, a decyltriphenyl phosphonium cation conjugated to a quinone moiety, produced strong antibacterial effect on Gram-positive Bacillus subtilis, Mycobacterium sp. and Staphylococcus aureus and Gram-negative Photobacterium phosphoreum and Rhodobacter sphaeroides at submicromolar and micromolar concentrations. SkQ1 exhibited much lower antibiotic activity towards Escherichia coli obviously due to the presence of the highly effective multidrug resistance pump AcrAB-TolC. E. coli mutants lacking any of AcrAB-TolC transporter proteins showed similar SkQ1 sensitivity, as B. subtilis. To confirm that SkQ1 cations compete with ethidium for AcrAB-TolC as a transporter, we applied fluorescence correlation spectroscopy (FCS) for measuring ethidium accumulation in E. coli cells. By measuring fluorescence of the potential-sensitive dye DiS-C3-(5), we examined the effect of SkQ1 on the membrane potential of B. subtilis. Submicromolar concentrations of SkQ1 caused a decrease in the membrane potential of B. subtilis in the minute time scale, whereas 5 µM SkQ1 caused a rapid drop of membrane potential to the level observed with the channel-forming antibiotic gramicidin A. SkQ1 did not cause an increase in fluorescence of the cell membrane-impermeant probe propidium iodide, therefore the action of SkQ1 on the membrane potential of B. subtilis was not due to a detergent effect on bacterial membrane. The mechanism of SkQ1 toxicity towards bacterial cells was neither associated with DNA damage, nor with inhibition of translation. Lowering of the bacterial membrane potential by SkQ1 might be involved in the mechanism of its bactericidal action. No significant cytotoxic effect on mammalian HeLa cells was observed at bacteriotoxic concentrations of SkQ1. Therefore, SkQ1 may be effective in protection of the infected mammals by killing invading bacteria.