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.
Hirata
T
T
Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Japan.
Wakatabe
R
R
Nielsen
J
J
Someya
Y
Y
Fujihira
E
E
Kimura
T
T
Yamaguchi
A
A
D017920:Antiporters / Q000037:antagonists & inhibitors* / Q000235:genetics; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D002250:Carbon Radioisotopes; D006863:Hydrogen-Ion Concentration; D007189:Indans / Q000494:pharmacology*; D007700:Kinetics; D008744:Methylamines / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism; D013752:Tetracycline / Q000378:metabolism; D014316:Tritium
C107655:1,1-dimethyl-5-(1-hydroxypropyl)-4,6,7-trimethylindan; D017920:Antiporters; D001426:Bacterial Proteins; D002250:Carbon Radioisotopes; D007189:Indans; D008744:Methylamines; C079051:tetA protein, Bacteria; D014316:Tritium; C027451:methylamine; D013752:Tetracycline