REGULATION OF AN ANTIBIOTIC RESISTANCE DETERMINANT

这项建议是为了在基因控制的一般领域进行研究。 强调基因表达调控的机制 对病原菌和细菌的抗生素耐药性负责 具有重要经济意义的生物体用来合成这些 发酵产生的抗生素。我们正在研究的特定系统赋予了 对红霉素和相关抑制细菌的抗生素的耐药性 通过与核糖体结合来合成蛋白质。在这两组生物体中， 抗药性的表达可以由抗生素本身诱导，而 诱导的生化变化涉及23S核糖体的修饰 核糖核酸，靶标的一种结构成分 抗生素结合在一起。就致病细菌而言，了解 归纳规则允许我们预测，并有希望避免，形式 基于MLS抗生素选择能力的治疗失败 构成突变。就产生抗生素的有机体而言， 这些相同的诱导机制似乎与 致力于抗生素合成。这项研究的结果 建议的内容将直接与建立 合理使用MLS抗生素，而平行研究的结果是 抗生素生产商可诱导的MLS耐药性建议改进方法 这些生物体产生的抗生素。

This proposal is for research in the general area of gene control mechanisms with emphasis on the regulation of expression of a gene responsible for antibiotic resistance both in pathogenic bacteria and in the organisms that are of economic importance used to synthesize these antibiotics by fermentation. The specific system we are studing confers resistance to erythromycin and related antibiotics that inhibit bacterial protein synthesis by binding to the ribosome. In both groups of organisms, expression of resistance can be induced by the antibiotic itself, and the induced biochemical alternation involves a modification of 23S ribosomal ribonucleic acid, a structural component of the target to which the antibiotic binds. In the case of pathogenic bacteria, understanding the rules of induction permits us to predict, and hopefully avoid, forms of therapeutic failure based on the ability of MLS antibiotics to select constitutive mutants. In the case of the antibiotic-producing organisms, these same induction mechanisms appear to operate in conjunction with the commitment to antibiotic synthesis. The results obtained from the research proposed will be directly pertinent to establishing standards for the rational use of MLS antibiotics, while results from parallel studies of inducible MLS resistance in antibiotic producers suggest ways of improving antibiotic production by these organisms.