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 Ciofu, O.
Right arrow Articles by Høiby, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ciofu, O.
Right arrow Articles by Høiby, N.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2005, p. 2276-2282, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2276-2282.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Occurrence of Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Patients Is Associated with the Oxidative Stress Caused by Chronic Lung Inflammation

Oana Ciofu,1* Bente Riis,2 Tacjana Pressler,3 Henrik Enghusen Poulsen,2 and Niels Høiby1,4

Institute for Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Copenhagen, Denmark,1 Institute of Clinical Pharmacology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark,2 Cystic Fibrosis Center, Pediatric Department, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark,3 Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark4

Received 2 August 2004/ Returned for modification 7 October 2004/ Accepted 22 February 2005

Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation of the bacterial DNA by ROS presents an increased risk for the occurrence of hypermutable P. aeruginosa. The occurrence of hypermutable P. aeruginosa isolates was investigated directly in the sputum of 79 CF patients and among 141 isolates collected from 11 CF patients (10 to 15 isolates/patient) collected from the 1st and up to the 25th year of their chronic lung infection. The level of oxidized guanine moiety 8-oxo-2'-deoxyguanosine (8-oxodG), which is a frequently investigated DNA oxidative lesion, was measured. Hypermutable P. aeruginosa isolates were found in the sputum bacterial population of 54.4% of the CF patients. The earliest mutator P. aeruginosa isolates were found after 5 years from the onset of the chronic lung infection, and once they were present in the CF lung, the prevalence increased with time. The hypermutable isolates were significantly more resistant to antipseudomonal antibiotics than nonhypermutable isolates (P ≤ 0.001). The level of 8-oxodG/106 deoxyguanosine (dG) was significantly higher in hypermutable P. aeruginosa isolates (87 ± 38) than in nonhypermutable P. aeruginosa isolates (59.4 ± 17) (P = 0.02), and an increase to 86.84 from 21.65 8-oxodG/106 dG was found after exposure of the reference strain PAO1 to activated PMNs. Our results suggest that the chronic PMN inflammation in the CF lung promotes oxidative stress and is associated with the occurrence of hypermutable bacteria in the lung. The hypermutable phenotype can associate with mutations that confer adaptation of the bacteria in the lung and persistence of the infection.

* Corresponding author. Mailing address: University of Copenhagen, Panum Institute, IMMI 24.1, Blegdamsvej 3, 2200 Copenhagen N, Denmark. Phone: 45 35 32 78 99. Fax: 45 35 32 76 93. E-mail: O.Ciofu{at}immi.ku.dk.

Antimicrobial Agents and Chemotherapy, June 2005, p. 2276-2282, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2276-2282.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • van Gennip, M., Moser, C., Christensen, L. D., Bjarnsholt, T., Calum, H., Jensen, P. O., Christophersen, L., Hougen, H. P., Ciofu, O., Molin, S., Givskov, M., Hoiby, N. (2009). Augmented effect of early antibiotic treatment in mice with experimental lung infections due to sequentially adapted mucoid strains of Pseudomonas aeruginosa. J Antimicrob Chemother 64: 1241-1250 [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]  
  • Dotsch, A., Becker, T., Pommerenke, C., Magnowska, Z., Jansch, L., Haussler, S. (2009). Genomewide Identification of Genetic Determinants of Antimicrobial Drug Resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53: 2522-2531 [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]  
  • Wiegand, I., Marr, A. K., Breidenstein, E. B. M., Schurek, K. N., Taylor, P., Hancock, R. E. W. (2008). Mutator Genes Giving Rise to Decreased Antibiotic Susceptibility in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52: 3810-3813 [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]  
  • Driffield, K., Miller, K., Bostock, J. M., O'Neill, A. J., Chopra, I. (2008). Increased mutability of Pseudomonas aeruginosa in biofilms. J Antimicrob Chemother 61: 1053-1056 [Abstract] [Full Text]  
  • Perry, J. D., Laine, L., Hughes, S., Nicholson, A., Galloway, A., Gould, F. K. (2008). Recovery of antimicrobial-resistant Pseudomonas aeruginosa from sputa of cystic fibrosis patients by culture on selective media. J Antimicrob Chemother 61: 1057-1061 [Abstract] [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]  
  • Sandoz, K. M., Mitzimberg, S. M., Schuster, M. (2007). From the Cover: Social cheating in Pseudomonas aeruginosa quorum sensing. Proc. Natl. Acad. Sci. USA 104: 15876-15881 [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]  
  • Harrison, F., Buckling, A. (2007). High relatedness selects against hypermutability in bacterial metapopulations. Proc R Soc B 274: 1341-1347 [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]  
  • Harrison, F. (2007). Microbial ecology of the cystic fibrosis lung. Microbiology 153: 917-923 [Abstract] [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»