Transcriptome profiling in imipenem-selected Acinetobacter baumannii

BMC Genomics

Ming-Li Liou⁴  Kuan-Hsueh Chen³  Huei-Ru Lin⁵  Chih-Chin Liu¹  Chia-Wei Lu²  Cheng-Wei Chang³  Chuan Yi Tang²  Han-Yueh Kuo⁶  Kai-Chih Chang⁵ 

[1] Department of Bioinformatics, Chung Hua University, Hsin-Chu City, Taiwan;Department of Computer Science, National Tsing Hua University, Hsin-Chu City, Taiwan;Department of Computer Science and Information Engineering, Providence University, Taichung, Taichung County, Taiwan;Department of Medical Laboratory Science and Biotechnology, Yuanpei University, No. 306, Yuanpei Street, Hsin-Chu 30015, Taiwan;Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien City, Taiwan;College of Medicine, National Taiwan University, Taipei City, Taiwan

关键词: Transcriptome profiling;    Carbapenem resistance;    Acinetobacter baumannii;   

Others  :  1139516
DOI  :  10.1186/1471-2164-15-815

 received in 2014-05-11, accepted in 2014-09-18,  发布年份 2014

【 摘 要 】

Background

Carbapenem-resistance in Acinetobacter baumannii has gradually become a global challenge. To identify the genes involved in carbapenem resistance in A. baumannii, the transcriptomic responses of the completely sequenced strain ATCC 17978 selected with 0.5 mg/L (IPM-2 m) and 2 mg/L (IPM-8 m) imipenem were investigated using RNA-sequencing to identify differences in the gene expression patterns.

Results

A total of 88 and 68 genes were differentially expressed in response to IPM-2 m and IPM-8 m selection, respectively. Among the expressed genes, 50 genes were highly expressed in IPM-2 m, 30 genes were highly expressed in IPM-8 m, and 38 genes were expressed common in both strains. Six groups of genes were simultaneously expressed in IPM-2 m and IPM-8 m mutants. The three gene groups involved in DNA recombination were up-regulated, including recombinase, transposase and DNA repair, and beta-lactamase OXA-95 and homologous recombination. The remaining gene groups involved in biofilm formation were down-regulated, including quorum sensing, secretion systems, and the csu operon. The antibiotic resistance determinants, including RND efflux transporters and multidrug resistance pumps, were over-expressed in response to IPM-2 m selection, followed by a decrease in response to IPM-8 m selection. Among the genes over-expressed in both strains, bla_OXA-95, previously clustered with the bla_OXA-51-like family, showed 14-fold (IPM-2 m) to 330-fold (IPM-8 m) over-expression. The expression of bla_OXA-95 in IPM-2 m and IPM-8 m cells was positively correlated with the rate of imipenem hydrolysis, as demonstrated through Liquid Chromatography-Mass Spectrometry/Mass Spectrometry, suggesting that bla_OXA-95 plays a critical role in conferring carbapenem resistance. In addition, A. baumannii shows an inverse relationship between carbapenem resistance and biofilm production.

Conclusion

Gene recombination and bla_OXA-95 play critical roles in carbapenem resistance in A. baumannii. Taken together, the results of the present study provide a foundation for future studies of the network systems associated with carbapenem resistance.

【 授权许可】

   
2014 Chang et al.; licensee BioMed Central Ltd.

【 图 表 】

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