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 Gillis, R. J.
Right arrow Articles by Iglewski, B. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gillis, R. J.
Right arrow Articles by Iglewski, B. H.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2005, p. 3858-3867, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3858-3867.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Molecular Basis of Azithromycin-Resistant Pseudomonas aeruginosa Biofilms{dagger}

Richard J. Gillis,1 Kimberly G. White,2 Kyoung-Hee Choi,2 Victoria E. Wagner,1 Herbert P. Schweizer,2 and Barbara H. Iglewski1*

Department of Microbiology and Immunology, University of Rochester, Rochester, New York,1 Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado2

Received 4 November 2004/ Returned for modification 6 January 2005/ Accepted 15 June 2005

Pseudomonas aeruginosa biofilms are extremely recalcitrant to antibiotic treatment. Treatment of cystic fibrosis patients with azithromycin (AZM) has shown promise. We used DNA microarrays to identify differentially expressed transcripts in developing P. aeruginosa biofilms exposed to 2 µg/ml AZM. We report that transcripts for multiple restriction-nodulation-cell division (RND) efflux pumps, known to be involved in planktonic antibiotic resistance, and transcripts involved in type III secretion were upregulated in the resistant biofilms that developed in the presence of AZM. Interestingly, the MexAB-OprM and MexCD-OprJ efflux pumps, but not type III secretion, appear to be integral to biofilm formation in the presence of AZM, as evidenced by the fact that a mutant deleted in both mexAB-oprM and mexCD-oprJ was unable to form a biofilm in the presence of AZM. A mutant deleted in type III secretion was still able to form biofilms in the presence of drug. Furthermore, single mexAB-oprM- and mexCD-oprJ-null mutants were able to form a biofilm in the presence of drug, indicating that either of the pumps can confer resistance to AZM during biofilm development. In contrast to planktonically grown cells, where no mexC expression was detectable regardless of the presence of AZM, biofilms exhibited induction of mexC expression from the outset of their formation, but only in the presence of AZM. mexA, which is constitutively expressed in planktonic cells, was uniformly expressed in biofilms regardless of the presence of AZM. These data indicate that the MexCD-OprJ pump acts as a biofilm-specific mechanism for AZM resistance.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Box 672, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642. Phone: (585) 275-3402. Fax: (585) 473-9573. E-mail: bigl{at}mail.rochester.edu.

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

Antimicrobial Agents and Chemotherapy, September 2005, p. 3858-3867, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3858-3867.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lister, P. D., Wolter, D. J., Hanson, N. D. (2009). Antibacterial-Resistant Pseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms. Clin. Microbiol. Rev. 22: 582-610 [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]  
  • Kvist, M., Hancock, V., Klemm, P. (2008). Inactivation of Efflux Pumps Abolishes Bacterial Biofilm Formation. Appl. Environ. Microbiol. 74: 7376-7382 [Abstract] [Full Text]  
  • Zhang, L., Mah, T.-F. (2008). Involvement of a Novel Efflux System in Biofilm-Specific Resistance to Antibiotics. J. Bacteriol. 190: 4447-4452 [Abstract] [Full Text]  
  • Vos, R., Vanaudenaerde, B. M., Geudens, N., Dupont, L. J., Van Raemdonck, D. E., Verleden, G. M. (2008). Pseudomonal airway colonisation: risk factor for bronchiolitis obliterans syndrome after lung transplantation?. Eur Respir J 31: 1037-1045 [Abstract] [Full Text]  
  • Starner, T. D., Shrout, J. D., Parsek, M. R., Appelbaum, P. C., Kim, G. (2008). Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation and Diminish Established Biofilms. Antimicrob. Agents Chemother. 52: 137-145 [Abstract] [Full Text]  
  • Lynch, S. V., Dixon, L., Benoit, M. R., Brodie, E. L., Keyhan, M., Hu, P., Ackerley, D. F., Andersen, G. L., Matin, A. (2007). Role of the rapA Gene in Controlling Antibiotic Resistance of Escherichia coli Biofilms. Antimicrob. Agents Chemother. 51: 3650-3658 [Abstract] [Full Text]  
  • Junker, L. M., Peters, J. E., Hay, A. G. (2006). Global analysis of candidate genes important for fitness in a competitive biofilm using DNA-array-based transposon mapping.. Microbiology 152: 2233-2245 [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»