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 noncompetitive, Although this compound caused membrane de-energization at a high concentration, the IC50 value for de-energization (7.3 mu mol/mg membrane protein) was about 17 times and 33 times higher than the values for Tet(K)-mediated proton/tetracycline antiport and [H-3]tetracycline transport, respectively, indicating that the inhibitory action of Ro 07-3149 is not due to the uncoupling effect of the inhibitor. (C) 1997 Federation of European Biochemical Societies.