Weisblum B, Graham M Y, Gryczan T, Dubnau D
J Bacteriol. 1979 Jan;137(1):635-43. doi: 10.1128/jb.137.1.635-643.1979.
A plasmid, pE194, obtained from Staphylococcus aureus confers resistance to macrolide, lincosamide, and streptogramin type B ("MLS") antibiotics. For full expression, the resistance phenotype requires a period of induction by subinhibitory concentrations of erythromycin. A copy number in the range of 10 to 25 copies per cell is maintained during cultivation at 32 degrees C. It is possible to transfer pE194 to Bacillus subtilis by transformation. In B. subtilis, the plasmid is maintained at a copy number of approximately 10 per cell at 37 degrees C, and resistance is inducible. Tylosin, a macrolide antibiotic which resembles erythromycin structurally and to which erythromycin induces resistance, lacks inducing activity. Two types of plasmid mutants were obtained and characterized after selection on medium containing 10 microgram of tylosin per ml. One mutant class appeared to express resistance constitutively and maintained a copy number indistinguishable from that of the parent plasmid. The other mutant type had a 5- to 10-fold-elevated plasmid copy number (i.e., 50 to 100 copies per cell) and expressed resistance inducibly. Both classes of tylosin-resistant mutants were shown to be due to alterations in the plasmid and not to modifications of the host genome.
从金黄色葡萄球菌中获得的质粒pE194赋予对大环内酯类、林可酰胺类和B型链阳菌素（“MLS”）抗生素的抗性。为实现完全表达，抗性表型需要用亚抑制浓度的红霉素进行一段诱导期。在32℃培养期间，每个细胞中的拷贝数维持在10至25个拷贝的范围内。通过转化将pE194转移到枯草芽孢杆菌中是可行的。在枯草芽孢杆菌中，该质粒在37℃时每个细胞的拷贝数维持在约10个，并且抗性是可诱导的。泰乐菌素是一种大环内酯类抗生素，其在结构上与红霉素相似，且红霉素可诱导对其产生抗性，但泰乐菌素缺乏诱导活性。在含有每毫升10微克泰乐菌素的培养基上进行选择后，获得并鉴定了两种类型的质粒突变体。一类突变体似乎组成性地表达抗性，并且维持与亲本质粒难以区分的拷贝数。另一类突变体的质粒拷贝数升高了5至10倍（即每个细胞50至100个拷贝），并且可诱导地表达抗性。两类泰乐菌素抗性突变体均显示是由于质粒的改变而非宿主基因组的修饰所致。
