Malke H, Reichardt W, Hartmann M, Walter F
Antimicrob Agents Chemother. 1981 Jan;19(1):91-100. doi: 10.1128/AAC.19.1.91.
The phenomenon of zonal resistance to lincomycin, which is characteristic of most clinical isolates with lincomycin resistance in Streptococcus pyogenes, has been studied. These strains grow within a defined concentration range of lincomycin (approximately 60 to 200 microgram/ml), or at lincomycin concentrations below the minimal inhibitory concentration for susceptible strains. It is shown that the zonal growth phenomenon is a stable phenotype and results from induction of resistance only within the zonal concentration range of lincomycin. These strains also possess inducible resistance to erythromycin which is nonzonal in character. One-step mutations to constitutive resistance have been isolated which are of two types: constitutive for lincomycin or for erythromycin, but not for both. Those strains with constitutive erythromycin resistance retain their zonal resistance for lincomycin. Mutants doubly constitutive for both lincomycin and erythromycin can be obtained by a second mutational step from either of the singly constitutive mutants. Satellite deoxyribonucleic acid has been shown to be present in the zonal resistant strains. A plasmid, pSM10419, of 14.9 megadaltons, has been isolated from one of the doubly constitutive mutants and used to jointly transform Streptococcus sanguis strain Challis to constitutive resistance to both lincomycin and erythromycin. From this, a multicopy plasmid of reduced size, pSM10 (5.4 megadaltons), which retains its resistance phenotype, has been isolated and mapped with restriction endonucleases HindIII (three sites), EcoRI (one site), KpnI (one site), and HpaI (one site). The staphylococcal plasmid pC221 (2.9 megadaltons; chloramphenicol resistant) has been fused to pSM10 at the EcoRI site resulting in a chimeric plasmid, pSM10221 (8.3 megadaltons), which retains resistance to chloramphenicol, erythromycin, and lincomycin. pSM10 is therefore suggestive as an effective cloning vehicle for the genus Streptococcus.
对化脓性链球菌中大多数对林可霉素耐药的临床分离株所特有的林可霉素区域耐药现象进行了研究。这些菌株在林可霉素的特定浓度范围内（约60至200微克/毫升）生长，或在低于敏感菌株最小抑菌浓度的林可霉素浓度下生长。结果表明，区域生长现象是一种稳定的表型，仅在林可霉素的区域浓度范围内由耐药诱导产生。这些菌株还具有对红霉素的诱导性耐药，其性质是非区域性的。已分离出一步突变形成的组成型耐药突变株，有两种类型：对林可霉素或对红霉素组成型耐药，但不是两者都耐药。那些具有组成型红霉素耐药性的菌株对林可霉素仍保持区域耐药性。通过对任一单组成型突变株进行第二步突变，可获得对林可霉素和红霉素均为双组成型的突变株。已证明区域耐药菌株中存在卫星脱氧核糖核酸。从一个双组成型突变株中分离出一个14.9兆道尔顿的质粒pSM10419，并用于共同将血链球菌Challis菌株转化为对林可霉素和红霉素的组成型耐药。由此，分离出了一个大小减小的多拷贝质粒pSM10（5.4兆道尔顿），其保留了耐药表型，并用限制性内切酶HindIII（三个位点）、EcoRI（一个位点）、KpnI（一个位点）和HpaI（一个位点）进行了图谱分析。葡萄球菌质粒pC221（2.9兆道尔顿；耐氯霉素）已在EcoRI位点与pSM10融合，产生嵌合质粒pSM10221（8.3兆道尔顿），其保留了对氯霉素、红霉素和林可霉素的耐药性。因此，pSM10提示可作为链球菌属有效的克隆载体。
