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

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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.