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广泛耐药鲍曼不动杆菌 DU202 中抗菌药物耐药性的蛋白质基因组学特征

Proteogenomic characterization of antimicrobial resistance in extensively drug-resistant Acinetobacter baumannii DU202.

机构信息

Division of Life Science, Korea Basic Science Institute, Daejeon, 305-806 Daejeon, Korea.

Department of Biological Science, College of Natural Science, Dong-A University, Busan 604-714, Korea.

出版信息

J Antimicrob Chemother. 2014 Jun;69(6):1483-91. doi: 10.1093/jac/dku008. Epub 2014 Jan 31.

Abstract

OBJECTIVES

To determine the genomic sequence of extensively drug-resistant Acinetobacter baumannii DU202 and to perform proteomic characterization of antibiotic resistance in this strain using genome data.

METHODS

The genome sequence of A. baumannii DU202 was determined using the Hi-Seq 2000 system and comparative analysis was performed to determine the unique characteristics of A. baumannii DU202. Previous proteomic results from the cell wall membrane fraction by one-dimensional electrophoresis and liquid chromatography combined with mass spectrometry analysis (1DE-LC-MS/MS), using the A. baumannii ATCC 17978 genome as a reference, were reanalysed to elucidate the resistance mechanisms of A. baumannii DU202 using strain-specific genome data. Additional proteomic data from the cytosolic fraction were also analysed.

RESULTS

The genome of A. baumannii DU202 consists of 3660 genes and is most closely related to the Korean A. baumannii 1656-2 strain. More than 144 resistance genes were annotated in the A. baumannii DU202 genome, of which 72 that encoded proteins associated with antibiotic resistance were identified in the proteomic analysis of A. baumannii DU202 cultured in tetracycline, imipenem and Luria-Bertani broth (control) medium. Strong induction of β-lactamases, a multidrug resistance efflux pump and resistance-nodulation-cell division (RND) multidrug efflux proteins was found to be important in the antibiotic resistance responses of A. baumannii DU202.

CONCLUSIONS

Combining genomic and proteomic methods provided comprehensive information about the unique antibiotic resistance responses of A. baumannii DU202.

摘要

目的

确定广泛耐药鲍曼不动杆菌 DU202 的基因组序列,并利用基因组数据对该菌株的抗生素耐药性进行蛋白质组学特征分析。

方法

使用 Hi-Seq 2000 系统测定鲍曼不动杆菌 DU202 的基因组序列,并进行比较分析,以确定 DU202 的独特特征。先前使用一维电泳和液相色谱-质谱联用分析(1DE-LC-MS/MS)对细胞壁膜部分的蛋白质组学结果,以鲍曼不动杆菌 ATCC 17978 基因组作为参考,利用菌株特异性基因组数据对鲍曼不动杆菌 DU202 的耐药机制进行重新分析。还分析了细胞质部分的额外蛋白质组学数据。

结果

鲍曼不动杆菌 DU202 的基因组由 3660 个基因组成,与韩国鲍曼不动杆菌 1656-2 菌株最为密切相关。在鲍曼不动杆菌 DU202 基因组中注释了超过 144 个耐药基因,其中 72 个基因编码与抗生素耐药相关的蛋白质,这些蛋白质在四环素、亚胺培南和 Luria-Bertani 肉汤(对照)培养基中培养的鲍曼不动杆菌 DU202 的蛋白质组学分析中得到鉴定。发现β-内酰胺酶、多药耐药外排泵和耐药-结节-分裂(RND)多药外排蛋白的强烈诱导在鲍曼不动杆菌 DU202 的抗生素耐药反应中很重要。

结论

将基因组和蛋白质组学方法相结合,提供了关于鲍曼不动杆菌 DU202 独特抗生素耐药反应的全面信息。

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