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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
Author(s) -
Hirata Takahiro,
Wakatabe Rumi,
Nielsen Joergen,
Someya Yuichi,
Fujihira Erika,
Kimura Tomomi,
Yamaguchi Akihito
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00796-5
Subject(s) - antiporter , tetracycline , chemistry , membrane , membrane transport , stereochemistry , biochemistry , antibiotics
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 IC 50 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 [ 3 H]tetracycline transport, respectively, indicating that the inhibitory action of Ro 07‐3149 is not due to the uncoupling effect of the inhibitor.