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

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 micromol/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.