Screening of an inhibitor of the tetracycline efflux pump in a tetracycline-resistant clinical-isolate of Staphylococcus aureus 743.
Clinically-isolated methicillin-resistant Staphylococcus aureus (MRSA) strain 743 exhibited resistance to tetracycline as judged from the active efflux of the drug. The efflux of tetracycline was inhibited by an uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and minocycline. Inhibitors of the efflux pump were examined in this strain to determine the cellular accumulation of tetracycline. Out of seven compounds examined, three caused a significant increase in the cellular concentration of tetracycline by inhibiting the efflux pump. Two of them seem to be energy inhibitors. Ro 07-3149 inhibited the efflux pump without affecting the energy state, and exhibited very low antibacterial activity but showed weak synergy with tetracycline.
Nippon Roche Research Center, Kamakura, Kanagawa, Japan.
T
T
Hirata
R
R
Wakatabe
J
J
Nielsen
T
T
Satoh
S
S
Nihira
A
A
Yamaguchi
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D001692:Biological Transport; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D013752:Tetracycline / Q000378:metabolism* / Q000494:pharmacology; D013753:Tetracycline Resistance; D014475:Uncoupling Agents / Q000494:pharmacology
C107655:1,1-dimethyl-5-(1-hydroxypropyl)-4,6,7-trimethylindan; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007189:Indans; D008565:Membrane Proteins; D014475:Uncoupling Agents; C084212:tet(K) protein, Staphylococcus aureus; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D013752:Tetracycline; D008911:Minocycline