title: Transcriptome profiling in imipenem-selected Acinetobacter baumannii.
abstract: 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, blaOXA-95, previously clustered with the blaOXA-51-like family, showed 14-fold (IPM-2 m) to 330-fold (IPM-8 m) over-expression. The expression of blaOXA-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 blaOXA-95 plays a critical role in conferring carbapenem resistance. In addition, A. baumannii shows an inverse relationship between carbapenem resistance and biofilm production.
  
  
  CONCLUSIONS
  Gene recombination and blaOXA-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.
authors.forename: Kai-Chih
authors.initials: KC
authors.lastname: Chang
authors.forename: Han-Yueh
authors.initials: HY
authors.lastname: Kuo
authors.forename: Chuan Yi
authors.initials: CY
authors.lastname: Tang
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Chang
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Lu
authors.forename: Chih-Chin
authors.initials: CC
authors.lastname: Liu
authors.forename: Huei-Ru
authors.initials: HR
authors.lastname: Lin
authors.forename: Kuan-Hsueh
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Computer Science and Information Engineering, Providence University, Taichung, Taichung County, Taiwan. d918229@gmail.com.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Liou
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D006868:Hydrolysis; D015378:Imipenem / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D053719:Tandem Mass Spectrometry; D059467:Transcriptome; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015378:Imipenem; D001618:beta-Lactamases; C063912:carbapenemase