Amini Amon, Liu Mason, Ahmad Zulfiqar
Department of Biochemistry, Kirksville College of Osteopathic Medicine, A.T. Still University, Kirksville, MO 63501, USA.
Department of Biochemistry, Kirksville College of Osteopathic Medicine, A.T. Still University, Kirksville, MO 63501, USA.
Int J Biol Macromol. 2017 Aug;101:153-164. doi: 10.1016/j.ijbiomac.2017.03.087. Epub 2017 Mar 18.
The naturally occurring olive phenolics tyrosol, hydroxytyrosol, dihydroxyphenylglycol (DHPG), and oleuropein are known to have antioxidant, antitumor, and antibacterial properties. In the current study, we examined whether the antimicrobial properties of tyrosol, hydroxytyrosol, DHPG, and oleuropein were linked to the inhibition of bacterial ATP synthase. Tyrosol, hydroxytyrosol, DHPG, and oleuropein inhibited Escherichia coli wild-type and mutant membrane-bound FF ATP synthase to variable degrees. The growth properties of wild-type, null, and mutant strains in presence of above olive phenolics were also abrogated to variable degrees on limiting glucose and succinate. Tyrosol and oleuropein synergistically inhibited the wild-type enzyme. Comparative wild-type and mutant FF ATP synthase inhibitory profiles suggested that αArg-283 is an important residue and olive phenolics bind at the polyphenol binding pocket of ATP synthase. Growth patterns of wild-type, null, and mutant strains in the presence of tyrosol, hydroxytyrosol, DHPG, and oleuropein also hint at the possibility of additional molecular targets. Our results demonstrated that ATP synthase can be used as a molecular target and the antimicrobial properties of olive phenolics in general and tyrosol in particular can be linked to the binding and inhibition of bacterial ATP synthase.
天然存在的橄榄酚类物质酪醇、羟基酪醇、二羟基苯乙二醇（DHPG）和橄榄苦苷具有抗氧化、抗肿瘤和抗菌特性。在本研究中，我们检测了酪醇、羟基酪醇、DHPG和橄榄苦苷的抗菌特性是否与细菌ATP合酶的抑制作用有关。酪醇、羟基酪醇、DHPG和橄榄苦苷对大肠杆菌野生型和突变型膜结合FF ATP合酶有不同程度的抑制作用。在限制葡萄糖和琥珀酸存在的情况下，野生型、缺失型和突变型菌株在上述橄榄酚类物质存在时的生长特性也有不同程度的消除。酪醇和橄榄苦苷协同抑制野生型酶。野生型和突变型FF ATP合酶抑制谱的比较表明，αArg-283是一个重要残基，橄榄酚类物质结合在ATP合酶的多酚结合口袋处。野生型、缺失型和突变型菌株在酪醇、羟基酪醇、DHPG和橄榄苦苷存在时的生长模式也暗示了存在其他分子靶点的可能性。我们的结果表明，ATP合酶可作为一个分子靶点，一般来说橄榄酚类物质尤其是酪醇的抗菌特性可能与细菌ATP合酶的结合和抑制作用有关。
