Fujisawa Y, Weisblum B
J Bacteriol. 1981 May;146(2):621-31. doi: 10.1128/jb.146.2.621-631.1981.
Inducible resistance to macrolide, lincosamide, and streptogramin type B antibiotics in Streptomyces spp. comprises a family of diverse phenotypes in which characteristic subsets of the macrolide-lincosamide-streptogramin antibiotics induce resistance mediated by mono- or dimethylation of adenine, or both, in 23S ribosomal ribonucleic acid. In these studies, diverse patterns of induction specificity in Streptomyces and associated ribosomal ribonucleic acid changes are described. In Streptomyces fradiae NRRL 2702 erythromycin induced resistance to vernamycin B, whereas in Streptomyces hygroscopicus IFO 12995, the reverse was found: vernamycin B induced resistance to erythromycin. In a Streptomyces viridochromogenes (NRRL 2860) model system studied in detail, tylosin induced resistance to erythromycin associated with N6-monomethylation of 23S ribosomal ribonucleic acid, whereas in Staphylococcus aureus, erythromycin induced resistance to tylosin mediated by N6-dimethylation of adenine. Inducible macrolide-lincosamide-streptogramin resistance was found in S. fradiae NRRL 2702 and S. hygroscopicus IFO 12995, which synthesize the macrolides tylosin and maridomycin, respectively, as well as in the lincosamide producer Streptomyces lincolnensis NRRL 2936 and the streptogramin type B producer Streptomyces diastaticus NRRL 2560. A wide range of different macrolides including chalcomycin, tylosin, and cirramycin induced resistance when tested in an appropriate system. Lincomycin was active as inducer in S. lincolnensis, the organism by which it is produced, and streptogramin type B antibiotics induced resistance in S. fradiae, S. hygroscopicus, and the streptogramin type B producer S. diastaticus. Patterns of adenine methylation found included (i) lincomycin-induced monomethylation in S. lincolnensis (and constitutive monomethylation in a mutant selected with maridomycin), (ii) concurrent equimolar levels of adenine mono- plus dimethylation in S. hygroscopicus, (iii) monomethylation in S. fradiae (and dimethylation in a mutant selected with erythromycin), and (iv) adenine dimethylation in S. diastaticus induced by ostreogrycin B.
链霉菌属中对大环内酯类、林可酰胺类和B型链阳性菌素抗生素的诱导抗性包含一系列不同的表型，其中大环内酯 - 林可酰胺 - 链阳性菌素抗生素的特定亚组可诱导由23S核糖体核糖核酸中腺嘌呤的单甲基化或二甲基化，或两者介导的抗性。在这些研究中，描述了链霉菌中诱导特异性的不同模式以及相关的核糖体核糖核酸变化。在弗氏链霉菌NRRL 2702中，红霉素诱导对维纳霉素B的抗性，而在吸水链霉菌IFO 12995中则发现相反的情况：维纳霉素B诱导对红霉素的抗性。在一个经过详细研究的绿色产色链霉菌（NRRL 2860）模型系统中，泰乐菌素诱导对红霉素的抗性，这与23S核糖体核糖核酸的N6 - 单甲基化有关，而在金黄色葡萄球菌中，红霉素诱导由腺嘌呤的N6 - 二甲基化介导的对泰乐菌素的抗性。在分别合成大环内酯类泰乐菌素和马立霉素的弗氏链霉菌NRRL 2702和吸水链霉菌IFO 12995中，以及在林可酰胺产生菌林肯链霉菌NRRL 2936和B型链阳性菌素产生菌淀粉酶链霉菌NRRL 2560中，均发现了诱导性大环内酯 - 林可酰胺 - 链阳性菌素抗性。当在合适的系统中进行测试时，包括查耳霉素、泰乐菌素和曲张链丝霉素在内 的多种不同大环内酯类均可诱导抗性。林可霉素在其产生菌林肯链霉菌中作为诱导剂具有活性，而B型链阳性菌素抗生素在弗氏链霉菌、吸水链霉菌以及B型链阳性菌素产生菌淀粉酶链霉菌中可诱导抗性。所发现的腺嘌呤甲基化模式包括：（i）林肯链霉菌中林可霉素诱导的单甲基化（以及用马立霉素筛选出的突变体中的组成型单甲基化）；（ii）吸水链霉菌中等摩尔水平的腺嘌呤单甲基化和二甲基化同时存在；（iii）弗氏链霉菌中的单甲基化（以及用红霉素筛选出的突变体中的二甲基化）；（iv）奥氏菌素B诱导淀粉酶链霉菌中的腺嘌呤二甲基化。
