ИСТИНА

Mitochondria-targeted antioxidants are known to alleviate mitochondrial oxidative damage that causes a variety of diseases. We have found that SkQ1, a decyltriphenyl phosphonium cation conjugated to a quinone moiety, exerts a 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. Experiments with the potential-sensitive dye DiS-C3-(5) have shown that SkQ1 causes a decrease in the membrane potential of B. subtilis in the minute time scale at submicromolar concentrations, and a complete collapse of the bacterial membrane potential at micromolar concentrations. SkQ1 exhibits 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 display similar SkQ1 sensitivity, as B. subtilis. Mutants lacking AcrZ, a small membrane protein, associated with the multidrug efflux pump AcrB, are sensitive to many, but not all, of the antibiotics transported by AcrAB-TolC. By applying SkQ1-dependent bacterial growth suppression screening, we have shown that AcrZ is not required for removal of SkQ1 out of cells, and AcrABZ-TolC complex is not needed for removing SkQ1. It can be also concluded that amino acid residues of AcrZ are not involved in the formation of the binding site for SkQ1 on AcrAB-TolC.