REGULATION OF AN ANTIBIOTIC RESISTANCE DETERMINANT

这一建议是在基因控制的一般领域的研究 强调基因表达调控的机制 导致病原菌和细菌的抗生素耐药性， 那些具有重要经济价值的有机体用来合成这些 抗生素发酵 我们正在研究的特定系统赋予了 对红霉素和相关抗生素的抗性， 通过与核糖体结合来合成蛋白质。 在这两组生物中， 抗性的表达可由抗生素本身诱导， 诱导的生化变化涉及23S核糖体的修饰 核糖核酸是靶的结构成分， 抗生素结合。 在致病菌的情况下， 归纳法则允许我们预测，并希望避免， 基于MLS抗生素选择能力的治疗失败 组成型突变体。 在产生寄生虫的生物体的情况下， 这些相同的诱导机制似乎与 致力于抗生素合成。 从研究中获得的结果 建议将直接关系到建立标准， 合理使用MLS抗生素，而平行研究的结果 抗生素生产商中可诱导的MLS抗性提出了改善 抗生素的产生。

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.