Yanofsky C, Horn V
Department of Biological Sciences, Stanford University, California 94305-5020, USA.
J Bacteriol. 1995 Aug;177(15):4451-6. doi: 10.1128/jb.177.15.4451-4456.1995.
The growth-inhibiting drug bicyclomycin, known to be an inhibitor of Rho factor activity in Escherichia coli, was shown to increase basal level expression of the tryptophanase (tna) operon and to allow growth of a tryptophan auxotroph on indole. The drug also relieved polarity in the trp operon and permitted growth of a trp double nonsense mutant on indole. Nine bicyclomycin-resistant mutants were isolated and partially characterized. Recombination data and genetic and biochemical complementation analyses suggest that five have mutations that affect rho, three have mutations that affect rpoB, and one has a mutation that affects a third locus, near rpoB. Individual mutants showed decreased, normal, or increased basal-level expression of the tna operon. All but one of the resistant mutants displayed greatly increased tna operon expression when grown in the presence of bicyclomycin. The tna operon of the wild-type drug-sensitive parent was also shown to be highly expressed during growth with noninhibitory concentrations of bicyclomycin. These findings demonstrate that resistance to this drug may be required by mutations at any one of three loci, two of which appear to be rho and rpoB.
生长抑制药物双环霉素，已知是大肠杆菌中 Rho 因子活性的抑制剂，它能增加色氨酸酶（tna）操纵子的基础水平表达，并使色氨酸营养缺陷型在吲哚上生长。该药物还能缓解 trp 操纵子中的极性，并使 trp 双无义突变体在吲哚上生长。分离出九个对双环霉素耐药的突变体并进行了部分表征。重组数据以及遗传和生化互补分析表明，五个突变体的突变影响 rho，三个突变体的突变影响 rpoB，一个突变体的突变影响靠近 rpoB 的第三个位点。单个突变体显示 tna 操纵子的基础水平表达降低、正常或增加。除了一个耐药突变体外，所有其他突变体在双环霉素存在下生长时，tna 操纵子的表达都大幅增加。野生型对药物敏感的亲本的 tna 操纵子在非抑制浓度的双环霉素存在下生长时也显示出高表达。这些发现表明，对这种药物的抗性可能由三个位点中任何一个的突变引起，其中两个位点似乎是 rho 和 rpoB。
