Genetic study of plasmid-associated zonal resistance to lincomycin in Streptococcus pyogenes

Genetic study of plasmid-associated zonal resistance to lincomycin in Streptococcus pyogenes
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化脓性链球菌质粒相关林可霉素带状耐药性的遗传研究

DOI:
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发表时间:
1981
影响因子:
4.9
通讯作者:
F. Walter
F. Walter
中科院分区:
医学2区
文献类型:
--
作者:
H. Malke;W. Reichardt;M. Hartmann;F. Walter

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对林可霉素的区域性耐药现象是化脓性链球菌中大多数林可霉素耐药临床分离株的特征,已进行了研究。这些菌株在规定的林可霉素浓度范围(约60 - 200 μ g/ml)内生长,或在低于敏感菌株最低抑菌浓度的林可霉素浓度下生长。结果表明,带状生长现象是一个稳定的表型,结果从诱导耐药性只有在带状浓度范围内的林可霉素。这些菌株也具有诱导耐红霉素,这是非地带性的字符。已分离出两种类型的组成型耐药的一步突变:林可霉素组成型或红霉素组成型,但不是两者都组成型。那些具有组成性红霉素耐药的菌株保持其对林可霉素的区域耐药。林可霉素和红霉素的双组成型突变体可以通过第二突变步骤从任一单组成型突变体获得。卫星脱氧核糖核酸已被证明存在于区域耐药菌株中。已从一个双重组成型突变体中分离出14.9兆道尔顿的质粒pSM 10419,并将其用于联合转化血链球菌菌株查利斯,使其对林可霉素和红霉素都具有组成型抗性。由此,分离出保留其抗性表型的减小大小的多拷贝质粒pSM 10(5.4兆道尔顿),并用限制性内切酶HindIII(三个位点)、EcoRI(一个位点)、Kpn I(一个位点)和Hpa I(一个位点)作图。葡萄球菌质粒pC 221(2.9兆道尔顿;氯霉素抗性)在EcoRI位点与pSM 10融合,产生嵌合质粒pSM 10221(8.3兆道尔顿),其保留对氯霉素、红霉素和林可霉素的抗性。因此,pSM 10是链球菌属的有效克隆载体。
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.