Hirata T, Wakatabe R, Nielsen J, Satoh T, Nihira S, Yamaguchi A
Nippon Roche Research Center, Kamakura, Kanagawa, Japan.
Biol Pharm Bull. 1998 Jul;21(7):678-81. doi: 10.1248/bpb.21.678.
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.
临床分离的耐甲氧西林金黄色葡萄球菌（MRSA）菌株743表现出对四环素的耐药性，这是根据该药物的主动外排判断得出的。四环素的外排受到解偶联剂羰基氰化物间氯苯腙（CCCP）和米诺环素的抑制。在该菌株中检测了外排泵抑制剂，以确定四环素的细胞内蓄积情况。在所检测的七种化合物中，有三种通过抑制外排泵使四环素的细胞内浓度显著增加。其中两种似乎是能量抑制剂。Ro 07-3149抑制外排泵而不影响能量状态，其抗菌活性非常低，但与四环素表现出微弱的协同作用。
