A novel compound, 1,1‐dimethyl‐5‐(1‐hydroxypropyl)‐4,6,7‐trimethylindan, is an effective inhibitor of the tet(K) gene‐encoded metal‐tetracycline/H+ antiporter of Staphylococcus aureus

FEBS Letters

Someya, Yuichi²  Nielsen, Joergen³  Yamaguchi, Akihito²  Kimura, Tomomi²  Wakatabe, Rumi¹  Fujihira, Erika²  Hirata, Takahiro² 

[1] Nippon Roche Research Center, Kajiwara 200, Kamakura, Kanagawa 247, Japan;Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Mihogaoka, Ibaraki, Osaka 567, Japan;Hoffman-La Roche Ltd. 1, CH-4070 Basle, Switzerland

关键词: Ro 07-3149;    Tetracycline;    Antiporter;    TetK;    Staphylococcus aureus;    Ro 07-3149;    1;    1-dimethyl-5-(1-hydroxypropyl)-4;    6;    7-trimethylindan;    DMSO;    dimethyl sulfoxide;   

DOI  :  10.1016/S0014-5793(97)00796-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A novel indan derivative, 1,1-dimethyl-5-(1-hydroxypropyl)-4,6,7-trimethylindan (Ro 07-3149), was found to be a strong inhibitor of the tet(K) gene-encoded tetracycline/H⁺ antiporter of Staphylococcus aureus. One micromole of this compound per mg membrane protein was enough for complete inhibition of the Tet(K)-mediated tetracycline transport and tetracycline-coupled proton transport, without the energy state of the membrane being affected. The mode of inhibition was non-competitive. Although this compound caused membrane de-energization at a high concentration, the IC₅₀ value for de-energization (7.3 μmol/mg membrane protein) was about 17 times and 33 times higher than the values for Tet(K)-mediated proton/tetracycline antiport and [³H]tetracycline transport, respectively, indicating that the inhibitory action of Ro 07-3149 is not due to the uncoupling effect of the inhibitor.

【 授权许可】

Unknown