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 Maciá, M. D.
Right arrow Articles by Oliver, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maciá, M. D.
Right arrow Articles by Oliver, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2005, p. 3382-3386, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3382-3386.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Hypermutation Is a Key Factor in Development of Multiple-Antimicrobial Resistance in Pseudomonas aeruginosa Strains Causing Chronic Lung Infections

María D. Maciá,1 David Blanquer,2 Bernat Togores,2 Jaume Sauleda,2 José L. Pérez,1 and Antonio Oliver1*

Servicio de Microbiología,1 Servicio de Neumología, Hospital Son Dureta, Palma de Mallorca, Spain2

Received 2 March 2005/ Returned for modification 18 April 2005/ Accepted 6 May 2005

Pseudomonas aeruginosa is the most relevant pathogen producing chronic lung infections in patients with chronic underlying diseases such as cystic fibrosis (CF), bronchiectasis, and chronic obstructive pulmonary disease (COPD). Hypermutable (or mutator) P. aeruginosa strains, characterized by increased (up to 1,000-fold) spontaneous mutation rates due to alterations of the DNA mismatch repair (MMR) system have been found at high frequencies in the lungs of CF patients, but their role in other chronic processes is still unknown. Sixty-two P. aeruginosa isolates from 30 patients with underlying non-CF chronic respiratory diseases (22 with bronchiectasis and 8 with COPD) and documented chronic infection were studied. Antibiotic susceptibility profiles and mutation frequencies were determined, and complementation assays using the cloned wild-type mutS gene and molecular epidemiology studies (pulsed-field electrophoresis, [PFGE]) were performed with these strains. Thirty-three (53%) of the isolates were hypermutable, and 17 (57%) of the 30 patients were colonized by hypermutable strains. Strains from 11 of the 17 patients were found to be defective in the MMR mutS gene by complementation assays. Interpatient transmission of strains was ruled out by PFGE. Multiple-antimicrobial resistance was documented in 42% of the hypermutable strains in contrast to 0% resistance in the nonhypermutable strains (P < 0.0001). Hypermutable P. aeruginosa strains are extremely prevalent in chronic infections in contrast to what has been described in acute processes, suggesting a role of hypermutation in bacterial adaptation for long-term persistence. Furthermore, hypermutation is found to be a key factor for the development of multiple-antimicrobial resistance, and therefore these findings are expected to have important consequences for the treatment of chronic infections.

* Corresponding author. Mailing address: Servicio de Microbiología, Hospital Son Dureta, C. Andrea Doria No. 55, 07014 Palma de Mallorca, Spain. Phone: 34 971 175 185. Fax: 34 971 175 185. E-mail: aoliver{at}hsd.es.

Antimicrobial Agents and Chemotherapy, August 2005, p. 3382-3386, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3382-3386.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Martinez, J. L. (2009). The role of natural environments in the evolution of resistance traits in pathogenic bacteria. Proc R Soc B 276: 2521-2530 [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]  
  • Gillham, M. I., Sundaram, S., Laughton, C. R., Haworth, C. S., Bilton, D., Foweraker, J. E. (2009). Variable antibiotic susceptibility in populations of Pseudomonas aeruginosa infecting patients with bronchiectasis. J Antimicrob Chemother 63: 728-732 [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]  
  • Foweraker, J. (2009). Recent advances in the microbiology of respiratory tract infection in cystic fibrosis. Br Med Bull 89: 93-110 [Abstract] [Full Text]  
  • Rodriguez-Rojas, A., Blazquez, J. (2009). The Pseudomonas aeruginosa pfpI Gene Plays an Antimutator Role and Provides General Stress Protection. J. Bacteriol. 191: 844-850 [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]  
  • Waine, D. J., Honeybourne, D., Smith, E. G., Whitehouse, J. L., Dowson, C. G. (2008). Association between Hypermutator Phenotype, Clinical Variables, Mucoid Phenotype, and Antimicrobial Resistance in Pseudomonas aeruginosa. J. Clin. Microbiol. 46: 3491-3493 [Abstract] [Full Text]  
  • Besier, S., Zander, J., Kahl, B. C., Kraiczy, P., Brade, V., Wichelhaus, T. A. (2008). The Thymidine-Dependent Small-Colony-Variant Phenotype Is Associated with Hypermutability and Antibiotic Resistance in Clinical Staphylococcus aureus Isolates. Antimicrob. Agents Chemother. 52: 2183-2189 [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]  
  • Macia, M. D., Mena, A., Borrell, N., Perez, J. L., Oliver, A. (2007). Increased Susceptibility to Colistin in Hypermutable Pseudomonas aeruginosa Strains from Chronic Respiratory Infections. Antimicrob. Agents Chemother. 51: 4531-4532 [Full Text]  
  • Gutierrez, O., Juan, C., Cercenado, E., Navarro, F., Bouza, E., Coll, P., Perez, J. L., Oliver, A. (2007). Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Pseudomonas aeruginosa Isolates from Spanish Hospitals. Antimicrob. Agents Chemother. 51: 4329-4335 [Abstract] [Full Text]  
  • Henrichfreise, B., Wiegand, I., Pfister, W., Wiedemann, B. (2007). Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation. Antimicrob. Agents Chemother. 51: 4062-4070 [Abstract] [Full Text]  
  • Kirov, S. M., Webb, J. S., O'May, C. Y., Reid, D. W., Woo, J. K. K., Rice, S. A., Kjelleberg, S. (2007). Biofilm differentiation and dispersal in mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Microbiology 153: 3264-3274 [Abstract] [Full Text]  
  • Henrichfreise, B., Wiegand, I., Luhmer-Becker, I., Wiedemann, B. (2007). Development of Resistance in Wild-Type and Hypermutable Pseudomonas aeruginosa Strains Exposed to Clinical Pharmacokinetic Profiles of Meropenem and Ceftazidime Simulated In Vitro. Antimicrob. Agents Chemother. 51: 3642-3649 [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]  
  • Kenna, D. T., Doherty, C. J., Foweraker, J., Macaskill, L., Barcus, V. A., Govan, J. R. W. (2007). Hypermutability in environmental Pseudomonas aeruginosa and in populations causing pulmonary infection in individuals with cystic fibrosis. Microbiology 153: 1852-1859 [Abstract] [Full Text]  
  • Montanari, S., Oliver, A., Salerno, P., Mena, A., Bertoni, G., Tummler, B., Cariani, L., Conese, M., Doring, G., Bragonzi, A. (2007). Biological cost of hypermutation in Pseudomonas aeruginosa strains from patients with cystic fibrosis. Microbiology 153: 1445-1454 [Abstract] [Full Text]  
  • Mena, A., Macia, M. D., Borrell, N., Moya, B., de Francisco, T., Perez, J. L., Oliver, A. (2007). Inactivation of the Mismatch Repair System in Pseudomonas aeruginosa Attenuates Virulence but Favors Persistence of Oropharyngeal Colonization in Cystic Fibrosis Mice. J. Bacteriol. 189: 3665-3668 [Abstract] [Full Text]  
  • Lujan, A. M., Moyano, A. J., Segura, I., Argarana, C. E., Smania, A. M. (2007). Quorum-sensing-deficient (lasR) mutants emerge at high frequency from a Pseudomonas aeruginosa mutS strain. Microbiology 153: 225-237 [Abstract] [Full Text]  
  • McMahon, M. A. S., Xu, J., Moore, J. E., Blair, I. S., McDowell, D. A. (2007). Environmental Stress and Antibiotic Resistance in Food-Related Pathogens. Appl. Environ. Microbiol. 73: 211-217 [Abstract] [Full Text]  
  • Bosso, J. A, Mauldin, P. D, Steed, L. L (2006). Consequences of Combining Cystic Fibrosis- and Non-Cystic Fibrosis-Derived Pseudomonas aeruginosa Antibiotic Susceptibility Results in Hospital Antibiograms. The Annals of Pharmacotherapy 40: 1946-1949 [Abstract] [Full Text]  
  • Mason, A. J., Gasnier, C., Kichler, A., Prevost, G., Aunis, D., Metz-Boutigue, M.-H., Bechinger, B. (2006). Enhanced Membrane Disruption and Antibiotic Action against Pathogenic Bacteria by Designed Histidine-Rich Peptides at Acidic pH.. Antimicrob. Agents Chemother. 50: 3305-3311 [Abstract] [Full Text]  
  • Driffield, K. L., Bostock, J. M., Miller, K., O'Neill, A. J., Hobbs, J. K., Chopra, I. (2006). Evolution of extended-spectrum {beta}-lactamases in a MutS-deficient Pseudomonas aeruginosa hypermutator. J Antimicrob Chemother 58: 905-907 [Full Text]  
  • Hall, L. M. C., Henderson-Begg, S. K. (2006). Hypermutable bacteria isolated from humans - a critical analysis.. Microbiology 152: 2505-2514 [Abstract] [Full Text]  
  • Aichele, D., Schnare, M., Saake, M., Rollinghoff, M., Gessner, A. (2006). Expression and antimicrobial function of bactericidal permeability-increasing protein in cystic fibrosis patients.. Infect. Immun. 74: 4708-4714 [Abstract] [Full Text]  
  • Macia, M. D., Borrell, N., Segura, M., Gomez, C., Perez, J. L., Oliver, A. (2006). Efficacy and Potential for Resistance Selection of Antipseudomonal Treatments in a Mouse Model of Lung Infection by Hypermutable Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 50: 975-983 [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»