放线菌对多种氨基糖苷类抗生素耐药性的基础及应用研究：一位老专家的回忆。

Basic and applied research on multiple aminoglycoside antibiotic resistance of actinomycetes: an old-timer's recollection.

机构信息

Functional Water Foundation, 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

出版信息

J Ind Microbiol Biotechnol. 2021 Dec 23;48(9-10). doi: 10.1093/jimb/kuab059.

DOI:10.1093/jimb/kuab059

PMID:34402899

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8788812/

Abstract

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.

摘要

概述了我们在产生氨基糖苷抗生素（AG）的放线菌中对多种氨基糖苷抗生素耐药性（AGR）的研究成果。1979 年，作者通过筛选具有卡那霉素（KM）抗性和质粒图谱的放线菌，发现了一种新型的 AG（伊他霉素）产生链霉菌 S. tenjimariensis SS-939。这一发现引导我们对 AG 产生菌的多种 AG 耐药性（AGR）进行了生化和遗传研究。本文概述了以下发现：（1）与 AG 产生菌中 AG 生产力相关的 AGR 图谱，（2）AGR 在非 AG 产生放线菌中的广泛分布，（3）核糖体耐药性和 AG 乙酰化酶作为潜在 AGR 因素的参与，（4）通过沉默基因编码的氨基糖苷 3-N-乙酰转移酶（AAC(3)）的单核苷酸取代激活，（5）通过 S. tenjimariensis 和 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美辛，具有不同的 AGR 表型，（6）通过克隆的 AACs 对 ABK（一种抗 MRSA 的半合成 AG）进行乙酰化，发现了阿贝卡星（ABK；一种抗-MRSA 半合成 AG）的双重阶段作用活性；即 ABK 及其乙酰化衍生物均表现出显著的抗生素活性。