Study on membrane transport of halobacterial cells used as model cells for the transport investigation of pharmaceutical agents

1.高嗜盐菌Haloferax volcano ii中的P-糖蛋白样转运蛋白。P-糖蛋白（P-gp）是一种ATP驱动的转运蛋白，转运许多结构无关的疏水阳离子，如抗癌试剂和染料。我们已经分离出一种突变体，它甚至可以在含有高浓度抗癌试剂的培养基中生长，并表明耐药性是由于ATP驱动的P-gp样外排泵。当野生菌株（其外排活性很小）在过量葡萄糖的存在下培养时，外排活性明显增加。使用非代谢糖时未观察到增加。在各种氨基酸存在下培养时也观察到增加.沃氏盐藻的果糖运输。我们发现，果糖被火山血吸虫吸收，其吸收的驱动力是Na^+-电化学电势差。以前，我们也报道了葡萄糖在该细菌中的转运是与Na^+的同向转运。这些葡萄糖和果糖的Na^+共转运系统在细菌细胞中尚属首次报道。3.大肠杆菌、肠球菌和谷氨酸棒杆菌的多重耐药性。在此基础上，我们成功地分离出了这些细菌的突变株，这些突变株由于外排泵而表现出多重耐药。这些泵的特性可能是一个有趣的和富有成效的进一步调查。

1.P-glycoprotein-like transporter in highly halophilic bacterium, Haloferax volcanii. P-glycoprotein (P-gp) is a ATP-driven transporter for many structually-unrelated hydrophobic cations such as anti-cancer reagents and dyes. We have isolated an mutant which can grow even in a medium containing high concentrations of anti-cancer reagents and showed that the resistance is due to an ATP-driven P-gp-like efflux pump. When the wild strain (whose efflux activity is small) was cultured in the presence of excess glucose, the efflux activity increased appreciably. No increase was observed using non-metabolizing sugars. The increase was also observed when cultured in the presence of various amino acids.2. Fructose transport in Haloferax volcanii. We showed that the fructose is taken up by H.volcanii, whose driving force is Na^+-electrochemical potential difference. Previously, we also reported that glucose transport in this bacterium is a symport with Na^+. These Na^+-symport systems for glucose and fructose are the first report for bacterial cells.3.Multi-drug resistance in E.coli, Enterococcus hirae and corynebacterium glutamicum. On the basis of this research, we have succeeded in isolating mutants of these bacteria which shows multi-drug resistance due to efflux pump. Characterization of these pumps may be an interesting and fruitfull further investigation.