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 Henrichfreise, B.
Right arrow Articles by Wiedemann, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Henrichfreise, B.
Right arrow Articles by Wiedemann, B.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2007, p. 4062-4070, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00148-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation{triangledown} ,{dagger}

B. Henrichfreise,1* I. Wiegand,1 W. Pfister,2 and B. Wiedemann1

University of Bonn, Institute for Medical Microbiology, Immunology and Parasitology, Pharmaceutical Microbiology Unit, Meckenheimer Allee 168, 53115 Bonn, Germany,1 University of Jena, Institute for Medical Microbiology, Germany2

Received 1 February 2007/ Returned for modification 8 April 2007/ Accepted 1 September 2007

In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with ß-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

* Corresponding author. Mailing address: University of Bonn, Institute for Medical Microbiology, Immunology and Parasitology, Pharmaceutical Microbiology Unit, Meckenheimer Allee 168, 53115 Bonn, Germany. Phone: 49 228 732111. Fax: 49 228 735267. E-mail: bhenrich{at}uni-bonn.de

{triangledown} Published ahead of print on 17 September 2007.

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

Antimicrobial Agents and Chemotherapy, November 2007, p. 4062-4070, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00148-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rodriguez-Martinez, J.-M., Poirel, L., Nordmann, P. (2009). Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53: 4783-4788 [Abstract] [Full Text]  
  • Strahilevitz, J., Jacoby, G. A., Hooper, D. C., Robicsek, A. (2009). Plasmid-Mediated Quinolone Resistance: a Multifaceted Threat. Clin. Microbiol. Rev. 22: 664-689 [Abstract] [Full Text]  
  • Livermore, D. M. (2009). Has the era of untreatable infections arrived?. J Antimicrob Chemother 64: i29-i36 [Abstract] [Full Text]  
  • Baum, E. Z., Crespo-Carbone, S. M., Morrow, B. J., Davies, T. A., Foleno, B. D., He, W., Queenan, A. M., Bush, K. (2009). Effect of MexXY Overexpression on Ceftobiprole Susceptibility in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53: 2785-2790 [Abstract] [Full Text]  
  • Mandsberg, L. F., Ciofu, O., Kirkby, N., Christiansen, L. E., Poulsen, H. E., Hoiby, N. (2009). Antibiotic Resistance in Pseudomonas aeruginosa Strains with Increased Mutation Frequency Due to Inactivation of the DNA Oxidative Repair System. Antimicrob. Agents Chemother. 53: 2483-2491 [Abstract] [Full Text]  
  • Mulet, X., Macia, M. D., Mena, A., Juan, C., Perez, J. L., Oliver, A. (2009). Azithromycin in Pseudomonas aeruginosa Biofilms: Bactericidal Activity and Selection of nfxB Mutants. Antimicrob. Agents Chemother. 53: 1552-1560 [Abstract] [Full Text]  
  • Mena, A., Smith, E. E., Burns, J. L., Speert, D. P., Moskowitz, S. M., Perez, J. L., Oliver, A. (2008). Genetic Adaptation of Pseudomonas aeruginosa to the Airways of Cystic Fibrosis Patients Is Catalyzed by Hypermutation. J. Bacteriol. 190: 7910-7917 [Abstract] [Full Text]  
  • Moya, B., Juan, C., Alberti, S., Perez, J. L., Oliver, A. (2008). Benefit of Having Multiple ampD Genes for Acquiring {beta}-Lactam Resistance without Losing Fitness and Virulence in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52: 3694-3700 [Abstract] [Full Text]  
  • Martin, V., Domingo, E. (2008). Influence of the Mutant Spectrum in Viral Evolution: Focused Selection of Antigenic Variants in a Reconstructed Viral Quasispecies. Mol Biol Evol 25: 1544-1554 [Abstract] [Full Text]  
  • Juan, C., Gutierrez, O., Renom, F., Garau, M., Gallegos, C., Alberti, S., Perez, J. L., Oliver, A. (2008). Chronic Respiratory Infections by Mucoid Carbapenemase-Producing Pseudomonas aeruginosa Strains, a New Potential Public Health Problem. Antimicrob. Agents Chemother. 52: 2285-2286 [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»