This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hu, W. S.
Right arrow Articles by Lin, J.-F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hu, W. S.
Right arrow Articles by Lin, J.-F.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2007, p. 3844-3852, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.01512-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

An OXA-66/OXA-51-Like Carbapenemase and Possibly an Efflux Pump Are Associated with Resistance to Imipenem in Acinetobacter baumannii{triangledown} ,{dagger}

Wensi S. Hu,1* Shu-Man Yao,1 Chang-Phone Fung,2 Yi-Ping Hsieh,1 Chang-Pan Liu,3 and Jing-Fang Lin1

Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering,1 Institute of Tropical Medicine, and Department of Parasitology, School of Medicine, National Yang-Ming University,2 Division of Infectious Diseases, Department of Medicine, Mackay Memorial Hospital, Taipei, Taiwan3

Received 1 December 2006/ Returned for modification 8 January 2007/ Accepted 15 August 2007

We investigated the mechanisms involved in imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in imipenem-intermediate A. baumannii (IIAB) and imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in imipenem-susceptible A. baumannii (ISAB) strains. The 30-kDa protein was identified as an OXA-51-like carbapenemase using two-dimensional gel electrophoresis and mass spectrometry. Similar to other recent findings, blaOXA-51-like genes were found to exist in all 23 clinical strains; however, the transcript levels of blaOXA-51-like in the IIAB and IRAB were higher than in the ISAB strains using reverse transcriptase PCR (RT-PCR) and real-time RT-PCR assays. This change was due to the presence of an insertion sequence, ISAba1, upstream of blaOXA-51-like in the IIAB and IRAB strains that was not present in the ISAB strains. The introduction of blaOXA-66 (a blaOXA-51-like gene), identified in ISAB ab1254 and IRAB ab1266, into Escherichia coli TOP10 cells resulted in 3.95-fold and 7.90-fold elevations in resistance to imipenem, respectively. Furthermore, when ISAB ab8 and ISAB ab1254 and their in vitro-selected imipenem-resistant mutants ISAB ab8(r) and ISAB ab1254(r) were compared, the results showed no change in the blaOXA-66/blaOXA-51-like gene sequences, in expression of the gene, and in the outer membrane protein profiles. However, there was a four- to eightfold reduction in imipenem resistance upon adding carbonyl cyanide m-chlorophenylhydrazone. Taken together, these results suggest that the OXA-66/OXA-51-like carbapenemase contributes to intrinsic resistance to imipenem; however, drug export by an efflux pump may be more important and/or occur more frequently in imipenem-resistant A. baumannii. Furthermore, this is the first report of a Taiwanese strain of an OXA-66/OXA-51-like carbapenemase that confers imipenem resistance in A. baumannii.

* Corresponding author. Mailing address: Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, 155 Li-Nong St., Sec. 2, Peitou, Taipei 112, Taiwan. Phone: 886-2-28267151. Fax: 886-2-28264092. E-mail: huws{at}ym.edu.tw

{triangledown} Published ahead of print on 27 August 2007.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, November 2007, p. 3844-3852, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.01512-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Grobner, S., Linke, D., Schutz, W., Fladerer, C., Madlung, J., Autenrieth, I. B., Witte, W., Pfeifer, Y. (2009). Emergence of carbapenem-non-susceptible extended-spectrum {beta}-lactamase-producing Klebsiella pneumoniae isolates at the university hospital of Tubingen, Germany. J Med Microbiol 58: 912-922 [Abstract] [Full Text]  
  • Figueiredo, S., Poirel, L., Croize, J., Recule, C., Nordmann, P. (2009). In Vivo Selection of Reduced Susceptibility to Carbapenems in Acinetobacter baumannii Related to ISAba1-Mediated Overexpression of the Natural blaOXA-66 Oxacillinase Gene. Antimicrob. Agents Chemother. 53: 2657-2659 [Abstract] [Full Text]  
  • Lu, P.-L., Doumith, M., Livermore, D. M., Chen, T.-P., Woodford, N. (2009). Diversity of carbapenem resistance mechanisms in Acinetobacter baumannii from a Taiwan hospital: spread of plasmid-borne OXA-72 carbapenemase. J Antimicrob Chemother 63: 641-647 [Abstract] [Full Text]  
  • Nemec, A., Krizova, L., Maixnerova, M., Diancourt, L., van der Reijden, T. J. K., Brisse, S., van den Broek, P., Dijkshoorn, L. (2008). Emergence of carbapenem resistance in Acinetobacter baumannii in the Czech Republic is associated with the spread of multidrug-resistant strains of European clone II. J Antimicrob Chemother 62: 484-489 [Abstract] [Full Text]  
  • Bratu, S., Landman, D., Martin, D. A., Georgescu, C., Quale, J. (2008). Correlation of Antimicrobial Resistance with {beta}-Lactamases, the OmpA-Like Porin, and Efflux Pumps in Clinical Isolates of Acinetobacter baumannii Endemic to New York City. Antimicrob. Agents Chemother. 52: 2999-3005 [Abstract] [Full Text]  
  • Chen, T.-L., Wu, R. C.-C., Shaio, M.-F., Fung, C.-P., Cho, W.-L. (2008). Acquisition of a Plasmid-Borne blaOXA-58 Gene with an Upstream IS1008 Insertion Conferring a High Level of Carbapenem Resistance to Acinetobacter baumannii. Antimicrob. Agents Chemother. 52: 2573-2580 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»