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

1.高度嗜盐细菌中的p糖蛋白样转运体。p -糖蛋白（P-gp）是一种atp驱动的转运体，用于许多结构无关的疏水阳离子，如抗癌试剂和染料。我们已经分离出一个突变体，即使在含有高浓度抗癌试剂的培养基中也能生长，并表明抗性是由于atp驱动的p- gp样外排泵。当外排活性较小的野生菌株在过量葡萄糖的存在下培养时，外排活性明显增加。使用非代谢糖没有观察到增加。在各种氨基酸的存在下培养时，也观察到这种增加。火山盐柳中的果糖转运。结果表明，果糖被H.volcanii吸收，其驱动力是Na^+-电化学电位差。在此之前，我们也报道了这种细菌中的葡萄糖转运是Na^+的同体。这些葡萄糖和果糖的Na^+-共感系统是首次报道的细菌细胞。大肠杆菌、hirae肠球菌和谷氨酸棒状杆菌的多重耐药。在此基础上，我们成功地分离出了这些细菌由于外排泵而产生多重耐药的突变体。表征这些泵可能是一个有趣的和富有成效的进一步研究。

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.