Mutations in rrn encoding ribosomal RNA (rRNA) and rRNA modification often confer resistance to ribosome-targeting antibiotics by altering the site of their interaction with the small (30S) and large (50S) subunits of the bacterial ribosome. The highly conserved central loop of domain V of 23S rRNA (nucleotides 2042-2628 in Escherichia coli; the exact position varies by species) of the 50S subunit, which is implicated in peptidyl transferase activity, is known to be important in macrolide interactions and resistance. In this study, we identified an A2302T mutation in the rrnA-23S rRNA gene and an A2281G mutation in the rrnC-23S rRNA gene that were responsible for resistance to erythromycin in the model actinomycete Streptomyces coelicolor A3(2) and its close relative Streptomyces lividans 66, respectively. Interestingly, genetic and phenotypic characterization of the erythromycin-resistant mutants indicated a possibility that under coexistence of the 23S rRNA mutation and mutations in other genes, S. coelicolor A3(2) and S. lividans 66 can produce abundant amounts of the pigmented antibiotics actinorhodin and undecylprodigiosin depending on the combinations of mutations. Herein, we report the unique phenomenon occurring by unexpected characteristics of the 23S rRNA mutations that can affect the emergence of additional mutations probably with an upswing in spontaneous mutations and enrichment in their variations in Streptomyces strains. Further, we discuss a putative mechanism underlying secondary metabolite overproduction by Streptomyces strains with a 23S rRNA mutation conferring erythromycin resistance.

中文翻译：

---

链霉菌菌株具有23S rRNA突变的二级代谢产物过量生产的推定机制，赋予红霉素抗性。

编码核糖体RNA（rRNA）的rrn突变和rRNA修饰通常通过改变它们与细菌核糖体的小（30S）和大（50S）亚基相互作用的位点，赋予针对核糖体靶向抗生素的抗性。已知与肽基转移酶活性有关的50S亚基的23S rRNA的V结构域的高度保守的中心环（大肠杆菌中的核苷酸2042-2628；确切位置因物种而异）在大环内酯相互作用和抗性中很重要。在这项研究中，我们在模型放线菌天蓝色链霉菌A3（2）及其近亲链霉菌青霉菌中鉴定了rrnA-23S rRNA基因中的A2302T突变和rrnC-23S rRNA基因中的A2281G突变，它们对红霉素具有抗性。 66。有趣的是 红霉素抗性突变体的遗传和表型特征表明，在23S rRNA突变和其他基因突变共存的情况下，大肠杆菌coelicolor A3（2）和利维酵母S. lividans 66可以产生大量有色色素的放线菌素和十一烷基谷胱甘肽取决于突变的组合。在本文中，我们报道了由23S rRNA突变的意外特征引起的独特现象，该现象可能影响其他突变的出现，可能是自发突变的增加以及链霉菌菌株中其变异的富集。此外，我们讨论了链霉菌菌株具有赋予红霉素抗性的23S rRNA突变的次级代谢产物过量生产的推定机制。