摘要/Abstract

摘要： 目的·探究乙酰化修饰在细菌应对核糖体靶向抗生素胁迫下的作用。方法·通过肉汤稀释法检测嘌呤霉素、巴龙霉素、四环素和壮观霉素对于鼠伤寒沙门菌（Salmonella enterica serovar Typhimurium，S. Typhimurium）14028S的最低抑菌浓度 （minimum inhibitory concentration，MIC）。配置浓度低于各抗生素MIC的固体培养基。点板实验检测S. Typhimurium 14028S和3种乙酰化修饰相关基因敲除株［蛋白质乙酰转移酶（protein acetyltransferase，Pat）编码基因敲除株Δpat、烟酰胺腺嘌呤二核苷酸依赖性去乙酰化酶（NAD⁺-dependent protein deacylase，CobB）编码基因敲除株ΔcobB、乙酸激酶（acetate kinase，AckA）编码基因敲除株ΔackA］在不同抗生素浓度的固体培养基上的生长差异。结果·乙酰化程度升高（ΔackA），增加S. Typhimurium对嘌呤霉素的敏感性，但会减弱S. Typhimurium对巴龙霉素的敏感性；而乙酰化程度升高（ΔackA、ΔcobB）或降低（Δpat）均不影响S. Typhimurium对四环素和壮观霉素的敏感性。结论·乙酰化修饰影响细菌对核糖体靶向抗生素的敏感性，这种改变可能是通过核糖体蛋白的乙酰化修饰来调控的。
关键词: 乙酰化修饰, 核糖体, 核糖体靶向抗生素
Abstract:
Objective·To investigate the effects of acetylation on the bacterial susceptibility to ribosome-targeting antibiotics.
Methods·The minimum inhibitory concentrations (MICs) of puromycin, paromomycin, tetracycline and spectinomycin for Salmonella enterica serovar Typhimurium (S. Typhimurium) 14028S were determined by the broth dilution method. The solid mediums with concentration lower than MIC was prepared. The spot dilution assay was employed to determine the susceptibility of S. Typhimuriumstrain 14028S, protein acetyltransferase (pat) knockout strain (Δpat), NAD⁺-dependent protein deacylase (cobB) knockout strain (ΔcobB) and acetate kinase (ackA) knockout strain (ΔackA) to four kinds of ribosome-targeting antibiotics.
Results·Increase of acetylation (ΔackA) promoted the susceptibility of S. Typhimurium to puromycin, but promoted the resistance of S. Typhimurium to paromomycin. However, the sensitivity of S. Typhimurium to tetracycline and spectinomycin was not affected by the increase of acetylation (ΔackA or ΔcobB) or decrease of acetylation (Δpat).
Conclusion·Acetylation is involved in the susceptibility of S. Typhimurium to ribosome-targeting antibiotics, suggesting that acetylation of ribosomal proteins may contribute to bacterial antibiotic sensitivity.

Key words: acetylation, ribosome, ribosome-targeting antibiotics


PDF全文下载地址:

点我下载PDF