A list of our research achievements on multiple aminoglycoside antibiotic (AG) resistance in AG-producing actinomycetes is outlined. In 1979, the author discovered a novel AG (istamycin)-producing Streptomyces tenjimariensis SS-939 by screening actinomycetes with kanamycin (KM)-resistance and plasmid profiles. This discovery directed our biochemical and genetic approaches to multiple AG resistance (AGR) of AG producers. In this article, the following discoveries will be outlined: (1) AGR profiles correlating with the productivity of AGs in AG-producers, (2) Wide distribution of multiple AG resistance in AG-nonproducing actinomycetes, (3) Involvement of ribosomal resistance and AG-acetylating enzymes as underlying AGR factors, (4) Activation by single nucleotide substitution of a silent gene coding for aminoglycoside 3-N-acetyltransferase, AAC(3), in S. griseus, (5) Discovery of a novel antibiotic indolizomycin through protoplast fusion treatment between S. tenjimariensis and S. griseus strains with different AGR phenotypes, and (6) Double stage-acting activity of arbekacin (ABK; an anti-MRSA semisynthetic AG) discovered by acetylation of ABK with cloned AACs; that is both ABK and its acetylated derivatives showed remarkable antibiotic activities.

中文翻译：

---

放线菌对多种氨基糖苷类抗生素耐药的基础与应用研究：前人回忆

概述了我们在产生 AG 的放线菌中对多种氨基糖苷类抗生素 (AG) 耐药的研究成果。1979 年，作者通过筛选具有卡那霉素 (KM) 抗性和质粒谱的放线菌，发现了一种新的产 AG (istamycin) 链霉菌 SS-939。这一发现指导了我们对 AG 生产者的多重 AG 抗性 (AGR) 的生化和遗传方法。在本文中，将概述以下发现：（1）与 AG 生产者中 AG 生产力相关的 AGR 概况，（2）不生产 AG 的放线菌中多种 AG 抗性的广泛分布，（3）核糖体抗性的参与和AG-乙酰化酶作为潜在的 AGR 因子，(4) 通过编码氨基糖苷 3-N-乙酰转移酶 AAC(3) 的沉默基因的单核苷酸替代激活，在 S. griseus 中，(5) 通过 S. tenjimariensis 和具有不同 AGR 表型的 S. griseus 菌株之间的原生质体融合处理发现了一种新型抗生素吲哚霉素，以及 (6) 阿贝卡星 (ABK; 一种抗 MRSA) 的双阶段作用活性通过用克隆的 AAC 乙酰化 ABK 发现的半合成 AG；即 ABK 及其乙酰化衍生物均显示出显着的抗生素活性。