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螺旋霉素对金黄色葡萄球菌耐药突变体的转录组特征分析螺旋霉素对金黄色葡萄球菌耐药突变体的转录组特征分析
投稿时间:2017-05-16  修订日期:2017-05-17  点此下载全文
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作者单位E-mail
姚健 中国药科大学 yj841104@163.com 
邵雷 上海医药工业研究院  
陈代杰 上海医药工业研究院  
张玉彬 中国药科大学 ybzhang@cpu.edu.cn 
基金项目:国家自然科学基金资助项目(No. 81573329)
中文摘要:螺旋霉素是一类重要的大环内酯类抗生素,但由于耐药菌的产生限制了临床使用。为了探讨其耐药机制,我们通过基于RNA-seq方法对螺旋霉素敏感菌株Staphylococcus aureus ATCC 29213和耐药突变菌株S.aureus ATCC 29213R进行了转录组表达分析。研究结果证明了螺旋霉素I可诱导Staphylococcus aureus ATCC 29213产生耐药菌株,并通过测序发现该菌的23S rRNA 2089位A→C颠换,,该位点突变在S. aureus中是首次报道。此外,还发现螺旋霉素能使S.aureus ATCC 29213R菌株的322个基因上调,82个基因下调,其中涉及精氨酸降解的基因arcA, arcC和argF表达水平分别上调35倍,18.05倍和30.84倍,涉及精氨酸合成的基因argH和argG分别下调13.51倍和 21.45倍,其综合作用减少精氨酸的内源性合成;因此,精氨酸代谢途径可能成为治疗23S RNA突变耐药金黄色葡萄球菌感染新的潜在靶点。
中文关键词:金黄色葡萄球菌  耐药性  螺旋霉素I  转录组分析  精氨酸代谢途径
 
Transcriptomic analysis of a spiramycin I-resistant Staphylococcus aureus mutant
Abstract:The clinical utility of macrolide antibiotics has declined due to the appearance of resistant isolates. A spiramycin I-resistant S. aureus ATCC29213R was induced and isolated with increasing the concentration of spiramycin I, which exhibits an A→C transversion at position 2089 in the 23S rRNA gene, which is first reported in the S. aureus. A RNA-seq based transcriptomic analysis was performed to understand the overall response of resistant bacteria to spiramycin I treatment with subinhibitory dosage. In this study, There are a total of 322 upregulated and 82 down-regulated genes in spiramycin I-treated S. aureus ATCC29213R and 426 up-regulated, 838 down-regulated in spiramycin I-treated S. aureus ATCC29213, which were identified differentially expressed compared to their control with a minimum 2-fold change (Q < 0.05). Interestingly, The data showed that argH and argG transcripts, in the arginine biosynthetic pathway, were decreased by 13.51-fold and 21.45-fold, respectively, compared to the control, while the expression level of three genes involved in arginine catabolism, arcA, arcC, and argF, increased by 35-fold, 18.05-fold and 30.84-fold, respectively. The results revealed that spiramycin I could trigger the up-regulation of the genes of ACME-Arc system which allows S. aureus to survive in acidic environments of human skin. This suggesed the arginine-deiminase pathway may be a potential target for treatment of the resistant S. aureus.
keywords:Staphylococcus aureus  antibiotic resistance  spiramycin I  transcriptome analyses  arginine metabolic pathways.
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