This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Langaee, T. Y.
Right arrow Articles by Huletsky, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Langaee, T. Y.
Right arrow Articles by Huletsky, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2000, p. 583-589, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Inactivation of the ampD Gene in Pseudomonas aeruginosa Leads to Moderate-Basal-Level and Hyperinducible AmpC beta -Lactamase Expression

Taimour Yousef Langaee, Luc Gagnon, and Ann Huletsky*

Centre de Recherche en Infectiologie, Université Laval, Québec, Canada G1V 4G2

Received 27 May 1999/Returned for modification 7 September 1999/Accepted 17 December 1999

It has been shown in enterobacteria that mutations in ampD provoke hyperproduction of chromosomal beta -lactamase, which confers to these organisms high levels of resistance to beta -lactam antibiotics. In this study, we investigated whether this genetic locus was implicated in the altered AmpC beta -lactamase expression of selected clinical isolates and laboratory mutants of Pseudomonas aeruginosa. The sequences of the ampD genes and promoter regions from these strains were determined and compared to that of wild-type ampD from P. aeruginosa PAO1. Although we identified numerous nucleotide substitutions, they resulted in few amino acid changes. The phenotypes produced by these mutations were ascertained by complementation analysis. The data revealed that the ampD genes of the P. aeruginosa mutants transcomplemented Escherichia coli ampD mutants to the same levels of beta -lactam resistance and beta -lactamase expression as wild-type ampD. Furthermore, complementation of the P. aeruginosa mutants with wild-type ampD did not restore the inducibility of beta -lactamase to wild-type levels. This shows that the amino acid substitutions identified in AmpD do not cause the altered phenotype of AmpC beta -lactamase expression in the P. aeruginosa mutants. The effects of AmpD inactivation in P. aeruginosa PAO1 were further investigated by gene replacement. This resulted in moderate-basal-level and hyperinducible expression of beta -lactamase accompanied by high levels of beta -lactam resistance. This differs from the stably derepressed phenotype reported in AmpD-defective enterobacteria and suggests that further change at another unknown genetic locus may be causing total derepressed AmpC production. This genetic locus could also be altered in the P. aeruginosa mutants studied in this work.

* Corresponding author. Mailing address: Centre de Recherche en Infectiologie, CHUQ, Pavillon CHUL, 2705, Boul. Laurier, RC-709, Ste-Foy, Québec, Canada G1V 4G2. Phone: (418) 654-2705. Fax: (418) 654-2715. E-mail: ann.huletsky{at}crchul.ulaval.ca.

Antimicrobial Agents and Chemotherapy, March 2000, p. 583-589, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, 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]  
  • Petrosino, J. F., Galhardo, R. S., Morales, L. D., Rosenberg, S. M. (2009). Stress-Induced {beta}-Lactam Antibiotic Resistance Mutation and Sequences of Stationary-Phase Mutations in the Escherichia coli Chromosome. J. Bacteriol. 191: 5881-5889 [Abstract] [Full Text]  
  • Strateva, T., Yordanov, D. (2009). Pseudomonas aeruginosa - a phenomenon of bacterial resistance. J Med Microbiol 58: 1133-1148 [Abstract] [Full Text]  
  • Schmidtke, A. J., Hanson, N. D. (2008). Role of ampD Homologs in Overproduction of AmpC in Clinical Isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52: 3922-3927 [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]  
  • Wolter, D. J., Schmidtke, A. J., Hanson, N. D., Lister, P. D. (2007). Increased Expression of ampC in Pseudomonas aeruginosa Mutants Selected with Ciprofloxacin. Antimicrob. Agents Chemother. 51: 2997-3000 [Abstract] [Full Text]  
  • Stubbs, K. A., Balcewich, M., Mark, B. L., Vocadlo, D. J. (2007). Small Molecule Inhibitors of a Glycoside Hydrolase Attenuate Inducible AmpC-mediated beta-Lactam Resistance. J. Biol. Chem. 282: 21382-21391 [Abstract] [Full Text]  
  • Plasencia, V., Borrell, N., Macia, M. D., Moya, B., Perez, J. L., Oliver, A. (2007). Influence of High Mutation Rates on the Mechanisms and Dynamics of In Vitro and In Vivo Resistance Development to Single or Combined Antipseudomonal Agents. Antimicrob. Agents Chemother. 51: 2574-2581 [Abstract] [Full Text]  
  • Bratu, S., Landman, D., Gupta, J., Quale, J. (2007). Role of AmpD, OprF and penicillin-binding proteins in {beta}-lactam resistance in clinical isolates of Pseudomonas aeruginosa. J Med Microbiol 56: 809-814 [Abstract] [Full Text]  
  • Reinhardt, A., Kohler, T., Wood, P., Rohner, P., Dumas, J.-L., Ricou, B., van Delden, C. (2007). Development and Persistence of Antimicrobial Resistance in Pseudomonas aeruginosa: a Longitudinal Observation in Mechanically Ventilated Patients. Antimicrob. Agents Chemother. 51: 1341-1350 [Abstract] [Full Text]  
  • Schmidtke, A. J., Hanson, N. D. (2006). Model System To Evaluate the Effect of ampD Mutations on AmpC-Mediated {beta}-Lactam Resistance.. Antimicrob. Agents Chemother. 50: 2030-2037 [Abstract] [Full Text]  
  • Juan, C., Moya, B., Perez, J. L., Oliver, A. (2006). Stepwise Upregulation of the Pseudomonas aeruginosa Chromosomal Cephalosporinase Conferring High-Level {beta}-Lactam Resistance Involves Three AmpD Homologues.. Antimicrob. Agents Chemother. 50: 1780-1787 [Abstract] [Full Text]  
  • Kong, K.-F., Jayawardena, S. R., Indulkar, S. D., del Puerto, A., Koh, C.-L., Hoiby, N., Mathee, K. (2005). Pseudomonas aeruginosa AmpR Is a Global Transcriptional Factor That Regulates Expression of AmpC and PoxB {beta}-Lactamases, Proteases, Quorum Sensing, and Other Virulence Factors. Antimicrob. Agents Chemother. 49: 4567-4575 [Abstract] [Full Text]  
  • Juan, C., Macia, M. D., Gutierrez, O., Vidal, C., Perez, J. L., Oliver, A. (2005). Molecular Mechanisms of {beta}-Lactam Resistance Mediated by AmpC Hyperproduction in Pseudomonas aeruginosa Clinical Strains. Antimicrob. Agents Chemother. 49: 4733-4738 [Abstract] [Full Text]  
  • Salunkhe, P., Smart, C. H. M., Morgan, J. A. W., Panagea, S., Walshaw, M. J., Hart, C. A., Geffers, R., Tummler, B., Winstanley, C. (2005). A Cystic Fibrosis Epidemic Strain of Pseudomonas aeruginosa Displays Enhanced Virulence and Antimicrobial Resistance. J. Bacteriol. 187: 4908-4920 [Abstract] [Full Text]  
  • Kaneko, K., Okamoto, R., Nakano, R., Kawakami, S., Inoue, M. (2005). Gene Mutations Responsible for Overexpression of AmpC {beta}-Lactamase in Some Clinical Isolates of Enterobacter cloacae. J. Clin. Microbiol. 43: 2955-2958 [Abstract] [Full Text]  
  • Bagge, N., Hentzer, M., Andersen, J. B., Ciofu, O., Givskov, M., Hoiby, N. (2004). Dynamics and Spatial Distribution of {beta}-Lactamase Expression in Pseudomonas aeruginosa Biofilms. Antimicrob. Agents Chemother. 48: 1168-1174 [Abstract] [Full Text]  
  • Weldhagen, G. F., Poirel, L., Nordmann, P. (2003). Ambler Class A Extended-Spectrum {beta}-Lactamases in Pseudomonas aeruginosa: Novel Developments and Clinical Impact. Antimicrob. Agents Chemother. 47: 2385-2392 [Full Text]  
  • Bagge, N., Ciofu, O., Hentzer, M., Campbell, J. I. A., Givskov, M., Hoiby, N. (2002). Constitutive High Expression of Chromosomal {beta}-Lactamase in Pseudomonas aeruginosa Caused by a New Insertion Sequence (IS1669) Located in ampD. Antimicrob. Agents Chemother. 46: 3406-3411 [Abstract] [Full Text]  
  • Petrosino, J. F., Pendleton, A. R., Weiner, J. H., Rosenberg, S. M. (2002). Chromosomal System for Studying AmpC-Mediated {beta}-Lactam Resistance Mutation in Escherichia coli. Antimicrob. Agents Chemother. 46: 1535-1539 [Abstract] [Full Text]  
  • Naas, T., Massuard, S., Garnier, F., Nordmann, P. (2001). AmpD Is Required for Regulation of Expression of NmcA, a Carbapenem-Hydrolyzing {beta}-Lactamase of Enterobacter cloacae. Antimicrob. Agents Chemother. 45: 2908-2915 [Abstract] [Full Text]  
  • Masuda, N., Sakagawa, E., Ohya, S., Gotoh, N., Nishino, T. (2001). Hypersusceptibility of the Pseudomonas aeruginosa nfxB Mutant to {beta}-Lactams Due to Reduced Expression of the AmpC {beta}-Lactamase. Antimicrob. Agents Chemother. 45: 1284-1286 [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»