Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 19 May 2000:
Vol. 288. no. 5469, pp. 1251 - 1253
DOI: 10.1126/science.288.5469.1251

Reports

High Frequency of Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Lung Infection

Antonio Oliver, Rafael Cantón, Pilar Campo, Fernando Baquero, * Jesús Blázquez *

The lungs of cystic fibrosis (CF) patients are chronically infected for years by one or a few lineages of Pseudomonas aeruginosa. These bacterial populations adapt to the highly compartmentalized and anatomically deteriorating lung environment of CF patients, as well as to the challenges of the immune defenses and antibiotic therapy. These selective conditions are precisely those that recent theoretical studies predict for the evolution of mechanisms that augment the rate of variation. Determination of spontaneous mutation rates in 128 P. aeruginosa isolates from 30 CF patients revealed that 36% of the patients were colonized by a hypermutable (mutator) strain that persisted for years in most patients. Mutator strains were not found in 75 non-CF patients acutely infected with P. aeruginosa. This investigation also reveals a link between high mutation rates in vivo and the evolution of antibiotic resistance.

Department of Microbiology and Unit for Cystic Fibrosis, Hospital Ramón y Cajal, National Institute of Health (INSALUD), 28034 Madrid, Spain.
*   To whom correspondence should be addressed. E-mail: fbaquero{at}hrc.insalud.es and jblazquez{at}hrc.insalud.es


Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
In Vitro Pharmacodynamics of Levofloxacin and Other Aerosolized Antibiotics under Multiple Conditions Relevant to Chronic Pulmonary Infection in Cystic Fibrosis.
P. King, O. Lomovskaya, D. C. Griffith, J. L. Burns, and M. N. Dudley (2010)
Antimicrob. Agents Chemother. 54, 143-148
   Abstract »    Full Text »    PDF »
Augmented effect of early antibiotic treatment in mice with experimental lung infections due to sequentially adapted mucoid strains of Pseudomonas aeruginosa.
M. van Gennip, C. Moser, L. D. Christensen, T. Bjarnsholt, H. Calum, P. O. Jensen, L. Christophersen, H. P. Hougen, O. Ciofu, S. Molin, et al. (2009)
J. Antimicrob. Chemother. 64, 1241-1250
   Abstract »    Full Text »    PDF »
Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia.
A. E. Morris, H. D. Liggitt, T. R. Hawn, and S. J. Skerrett (2009)
Am J Physiol Lung Cell Mol Physiol 297, L1112-L1119
   Abstract »    Full Text »    PDF »
The Glycerol-3-Phosphate Permease GlpT Is the Only Fosfomycin Transporter in Pseudomonas aeruginosa.
A. Castaneda-Garcia, A. Rodriguez-Rojas, J. R. Guelfo, and J. Blazquez (2009)
J. Bacteriol. 191, 6968-6974
   Abstract »    Full Text »    PDF »
Cross-Sectional and Longitudinal Multilocus Sequence Typing of Pseudomonas aeruginosa in Cystic Fibrosis Sputum Samples.
D. J. Waine, D. Honeybourne, E. G. Smith, J. L. Whitehouse, and C. G. Dowson (2009)
J. Clin. Microbiol. 47, 3444-3448
   Abstract »    Full Text »    PDF »
Role of lung iron in determining the bacterial and host struggle in cystic fibrosis.
D. W. Reid, G. J. Anderson, and I. L. Lamont (2009)
Am J Physiol Lung Cell Mol Physiol 297, L795-L802
   Abstract »    Full Text »    PDF »
Stress-Induced {beta}-Lactam Antibiotic Resistance Mutation and Sequences of Stationary-Phase Mutations in the Escherichia coli Chromosome.
J. F. Petrosino, R. S. Galhardo, L. D. Morales, and S. M. Rosenberg (2009)
J. Bacteriol. 191, 5881-5889
   Abstract »    Full Text »    PDF »
Genome-wide Mutational Diversity in an Evolving Population of Escherichia coli.
J.E. Barrick and R.E. Lenski (2009)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Has the era of untreatable infections arrived?.
D. M. Livermore (2009)
J. Antimicrob. Chemother. 64, i29-i36
   Abstract »    Full Text »    PDF »
The role of natural environments in the evolution of resistance traits in pathogenic bacteria.
J. L. Martinez (2009)
Proc R Soc B 276, 2521-2530
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa Microevolution during Cystic Fibrosis Lung Infection Establishes Clones with Adapted Virulence.
A. Bragonzi, M. Paroni, A. Nonis, N. Cramer, S. Montanari, J. Rejman, C. Di Serio, G. Doring, and B. Tummler (2009)
Am. J. Respir. Crit. Care Med. 180, 138-145
   Abstract »    Full Text »    PDF »
Antibiotic Resistance in Pseudomonas aeruginosa Strains with Increased Mutation Frequency Due to Inactivation of the DNA Oxidative Repair System.
L. F. Mandsberg, O. Ciofu, N. Kirkby, L. E. Christiansen, H. E. Poulsen, and N. Hoiby (2009)
Antimicrob. Agents Chemother. 53, 2483-2491
   Abstract »    Full Text »    PDF »
Genomewide Identification of Genetic Determinants of Antimicrobial Drug Resistance in Pseudomonas aeruginosa.
A. Dotsch, T. Becker, C. Pommerenke, Z. Magnowska, L. Jansch, and S. Haussler (2009)
Antimicrob. Agents Chemother. 53, 2522-2531
   Abstract »    Full Text »    PDF »
Inactivation of the hmgA gene of Pseudomonas aeruginosa leads to pyomelanin hyperproduction, stress resistance and increased persistence in chronic lung infection.
A. Rodriguez-Rojas, A. Mena, S. Martin, N. Borrell, A. Oliver, and J. Blazquez (2009)
Microbiology 155, 1050-1057
   Abstract »    Full Text »    PDF »
Azithromycin in Pseudomonas aeruginosa Biofilms: Bactericidal Activity and Selection of nfxB Mutants.
X. Mulet, M. D. Macia, A. Mena, C. Juan, J. L. Perez, and A. Oliver (2009)
Antimicrob. Agents Chemother. 53, 1552-1560
   Abstract »    Full Text »    PDF »
The Fixation Probability of Rare Mutators in Finite Asexual Populations.
C. S. Wylie, C.-M. Ghim, D. Kessler, and H. Levine (2009)
Genetics 181, 1595-1612
   Abstract »    Full Text »    PDF »
Recent advances in the microbiology of respiratory tract infection in cystic fibrosis.
J. Foweraker (2009)
Br. Med. Bull. 89, 93-110
   Abstract »    Full Text »    PDF »
The Pseudomonas aeruginosa pfpI Gene Plays an Antimutator Role and Provides General Stress Protection.
A. Rodriguez-Rojas and J. Blazquez (2009)
J. Bacteriol. 191, 844-850
   Abstract »    Full Text »    PDF »
Genetic Adaptation of Pseudomonas aeruginosa to the Airways of Cystic Fibrosis Patients Is Catalyzed by Hypermutation.
A. Mena, E. E. Smith, J. L. Burns, D. P. Speert, S. M. Moskowitz, J. L. Perez, and A. Oliver (2008)
J. Bacteriol. 190, 7910-7917
   Abstract »    Full Text »    PDF »
Novel Genetic Determinants of Low-Level Aminoglycoside Resistance in Pseudomonas aeruginosa.
K. N. Schurek, A. K. Marr, P. K. Taylor, I. Wiegand, L. Semenec, B. K. Khaira, and R. E. W. Hancock (2008)
Antimicrob. Agents Chemother. 52, 4213-4219
   Abstract »    Full Text »    PDF »
High prevalence in cystic fibrosis patients of multiresistant hospital-acquired methicillin-resistant Staphylococcus aureus ST228-SCCmecI capable of biofilm formation.
A. Molina, R. Del Campo, L. Maiz, M.-I. Morosini, A. Lamas, F. Baquero, and R. Canton (2008)
J. Antimicrob. Chemother. 62, 961-967
   Abstract »    Full Text »    PDF »
Mutator Genes Giving Rise to Decreased Antibiotic Susceptibility in Pseudomonas aeruginosa.
I. Wiegand, A. K. Marr, E. B. M. Breidenstein, K. N. Schurek, P. Taylor, and R. E. W. Hancock (2008)
Antimicrob. Agents Chemother. 52, 3810-3813
   Abstract »    Full Text »    PDF »
Phage-Associated Mutator Phenotype in Group A Streptococcus.
J. Scott, P. Thompson-Mayberry, S. Lahmamsi, C. J. King, and W. M. McShan (2008)
J. Bacteriol. 190, 6290-6301
   Abstract »    Full Text »    PDF »
Association between Hypermutator Phenotype, Clinical Variables, Mucoid Phenotype, and Antimicrobial Resistance in Pseudomonas aeruginosa.
D. J. Waine, D. Honeybourne, E. G. Smith, J. L. Whitehouse, and C. G. Dowson (2008)
J. Clin. Microbiol. 46, 3491-3493
   Abstract »    Full Text »    PDF »
Endogenous oxidative stress produces diversity and adaptability in biofilm communities.
B. R. Boles and P. K. Singh (2008)
PNAS 105, 12503-12508
   Abstract »    Full Text »    PDF »
Hydrogen Peroxide Linked to Lysine Oxidase Activity Facilitates Biofilm Differentiation and Dispersal in Several Gram-Negative Bacteria.
A. Mai-Prochnow, P. Lucas-Elio, S. Egan, T. Thomas, J. S. Webb, A. Sanchez-Amat, and S. Kjelleberg (2008)
J. Bacteriol. 190, 5493-5501
   Abstract »    Full Text »    PDF »
The Thymidine-Dependent Small-Colony-Variant Phenotype Is Associated with Hypermutability and Antibiotic Resistance in Clinical Staphylococcus aureus Isolates.
S. Besier, J. Zander, B. C. Kahl, P. Kraiczy, V. Brade, and T. A. Wichelhaus (2008)
Antimicrob. Agents Chemother. 52, 2183-2189
   Abstract »    Full Text »    PDF »
Chronic Respiratory Infections by Mucoid Carbapenemase-Producing Pseudomonas aeruginosa Strains, a New Potential Public Health Problem.
C. Juan, O. Gutierrez, F. Renom, M. Garau, C. Gallegos, S. Alberti, J. L. Perez, and A. Oliver (2008)
Antimicrob. Agents Chemother. 52, 2285-2286
   Full Text »    PDF »
Increased mutability of Pseudomonas aeruginosa in biofilms.
K. Driffield, K. Miller, J. M. Bostock, A. J. O'Neill, and I. Chopra (2008)
J. Antimicrob. Chemother. 61, 1053-1056
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa Cystic Fibrosis Isolates from Individual Patients Demonstrate a Range of Levels of Lethality in Two Drosophila melanogaster Infection Models.
E. I. Lutter, M. M. P. Faria, H. R. Rabin, and D. G. Storey (2008)
Infect. Immun. 76, 1877-1888
   Abstract »    Full Text »    PDF »
Signal-mediated interactions between Pseudomonas aeruginosa and Candida albicans.
G. McAlester, F. O'Gara, and J. P. Morrissey (2008)
J. Med. Microbiol. 57, 563-569
   Abstract »    Full Text »    PDF »
In Vivo Growth of Pseudomonas aeruginosa Strains PAO1 and PA14 and the Hypervirulent Strain LESB58 in a Rat Model of Chronic Lung Infection.
I. Kukavica-Ibrulj, A. Bragonzi, M. Paroni, C. Winstanley, F. Sanschagrin, G. A. O'Toole, and R. C. Levesque (2008)
J. Bacteriol. 190, 2804-2813
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa RsmA Plays an Important Role during Murine Infection by Influencing Colonization, Virulence, Persistence, and Pulmonary Inflammation.
H. Mulcahy, J. O'Callaghan, E. P. O'Grady, M. D. Macia, N. Borrell, C. Gomez, P. G. Casey, C. Hill, C. Adams, C. G. M. Gahan, et al. (2008)
Infect. Immun. 76, 632-638
   Abstract »    Full Text »    PDF »
Increased Susceptibility to Colistin in Hypermutable Pseudomonas aeruginosa Strains from Chronic Respiratory Infections.
M. D. Macia, A. Mena, N. Borrell, J. L. Perez, and A. Oliver (2007)
Antimicrob. Agents Chemother. 51, 4531-4532
   Full Text »    PDF »
Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Pseudomonas aeruginosa Isolates from Spanish Hospitals.
O. Gutierrez, C. Juan, E. Cercenado, F. Navarro, E. Bouza, P. Coll, J. L. Perez, and A. Oliver (2007)
Antimicrob. Agents Chemother. 51, 4329-4335
   Abstract »    Full Text »    PDF »
Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation.
B. Henrichfreise, I. Wiegand, W. Pfister, and B. Wiedemann (2007)
Antimicrob. Agents Chemother. 51, 4062-4070
   Abstract »    Full Text »    PDF »
The rise and spread of a new pathogen: Seroresistant Moraxella catarrhalis.
T. Wirth, G. Morelli, B. Kusecek, A. van Belkum, C. van der Schee, A. Meyer, and M. Achtman (2007)
Genome Res. 17, 1647-1656
   Abstract »    Full Text »    PDF »
From the Cover: Social cheating in Pseudomonas aeruginosa quorum sensing.
K. M. Sandoz, S. M. Mitzimberg, and M. Schuster (2007)
PNAS 104, 15876-15881
   Abstract »    Full Text »    PDF »
Biofilm differentiation and dispersal in mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis.
S. M. Kirov, J. S. Webb, C. Y. O'May, D. W. Reid, J. K. K. Woo, S. A. Rice, and S. Kjelleberg (2007)
Microbiology 153, 3264-3274
   Abstract »    Full Text »    PDF »
Development of Resistance in Wild-Type and Hypermutable Pseudomonas aeruginosa Strains Exposed to Clinical Pharmacokinetic Profiles of Meropenem and Ceftazidime Simulated In Vitro.
B. Henrichfreise, I. Wiegand, I. Luhmer-Becker, and B. Wiedemann (2007)
Antimicrob. Agents Chemother. 51, 3642-3649
   Abstract »    Full Text »    PDF »
Source-sink dynamics shape the evolution of antibiotic resistance and its pleiotropic fitness cost.
G. G Perron, A. Gonzalez, and A. Buckling (2007)
Proc R Soc B 274, 2351-2356
   Abstract »    Full Text »    PDF »
Identifying Mutator Phenotypes among Fluoroquinolone-Resistant Strains of Streptococcus pneumoniae Using Fluctuation Analysis.
C. V. Gould, P. D. Sniegowski, M. Shchepetov, J. P. Metlay, and J. N. Weiser (2007)
Antimicrob. Agents Chemother. 51, 3225-3229
   Abstract »    Full Text »    PDF »
Genetic Interactions of DNA Repair Pathways in the Pathogen Neisseria meningitidis.
T. Davidsen, H. K. Tuven, M. Bjoras, E. A. Rodland, and T. Tonjum (2007)
J. Bacteriol. 189, 5728-5737
   Abstract »    Full Text »    PDF »
Oxidative DNA Damage Defense Systems in Avoidance of Stationary-Phase Mutagenesis in Pseudomonas putida.
S. Saumaa, A. Tover, M. Tark, R. Tegova, and M. Kivisaar (2007)
J. Bacteriol. 189, 5504-5514
   Abstract »    Full Text »    PDF »
Influence of High Mutation Rates on the Mechanisms and Dynamics of In Vitro and In Vivo Resistance Development to Single or Combined Antipseudomonal Agents.
V. Plasencia, N. Borrell, M. D. Macia, B. Moya, J. L. Perez, and A. Oliver (2007)
Antimicrob. Agents Chemother. 51, 2574-2581
   Abstract »    Full Text »    PDF »
Hypermutability in environmental Pseudomonas aeruginosa and in populations causing pulmonary infection in individuals with cystic fibrosis.
D. T. Kenna, C. J. Doherty, J. Foweraker, L. Macaskill, V. A. Barcus, and J. R. W. Govan (2007)
Microbiology 153, 1852-1859
   Abstract »    Full Text »    PDF »
High relatedness selects against hypermutability in bacterial metapopulations.
F. Harrison and A. Buckling (2007)
Proc R Soc B 274, 1341-1347
   Abstract »    Full Text »    PDF »
Biological cost of hypermutation in Pseudomonas aeruginosa strains from patients with cystic fibrosis.
S. Montanari, A. Oliver, P. Salerno, A. Mena, G. Bertoni, B. Tummler, L. Cariani, M. Conese, G. Doring, and A. Bragonzi (2007)
Microbiology 153, 1445-1454
   Abstract »    Full Text »    PDF »
Inactivation of the Mismatch Repair System in Pseudomonas aeruginosa Attenuates Virulence but Favors Persistence of Oropharyngeal Colonization in Cystic Fibrosis Mice.
A. Mena, M. D. Macia, N. Borrell, B. Moya, T. de Francisco, J. L. Perez, and A. Oliver (2007)
J. Bacteriol. 189, 3665-3668
   Abstract »    Full Text »    PDF »
Quorum-sensing-deficient (lasR) mutants emerge at high frequency from a Pseudomonas aeruginosa mutS strain.
A. M. Lujan, A. J. Moyano, I. Segura, C. E. Argarana, and A. M. Smania (2007)
Microbiology 153, 225-237
   Abstract »    Full Text »    PDF »
Role of Pseudomonas aeruginosa dinB-Encoded DNA Polymerase IV in Mutagenesis.
L. H. Sanders, A. Rockel, H. Lu, D. J. Wozniak, and M. D. Sutton (2006)
J. Bacteriol. 188, 8573-8585
   Abstract »    Full Text »    PDF »
A paradigm for direct stress-induced mutation in prokaryotes.
J. M. Kang, N. M. Iovine, and M. J. Blaser (2006)
FASEB J 20, 2476-2485
   Abstract »    Full Text »    PDF »
Enhanced Membrane Disruption and Antibiotic Action against Pathogenic Bacteria by Designed Histidine-Rich Peptides at Acidic pH..
A. J. Mason, C. Gasnier, A. Kichler, G. Prevost, D. Aunis, M.-H. Metz-Boutigue, and B. Bechinger (2006)
Antimicrob. Agents Chemother. 50, 3305-3311
   Abstract »    Full Text »    PDF »
Weak Mutators Can Drive the Evolution of Fluoroquinolone Resistance in Escherichia coli..
H. Orlen and D. Hughes (2006)
Antimicrob. Agents Chemother. 50, 3454-3456
   Abstract »    Full Text »    PDF »
Candida albicans Strain Maintenance, Replacement, and Microvariation Demonstrated by Multilocus Sequence Typing..
F. C. Odds, A. D. Davidson, M. D. Jacobsen, A. Tavanti, J. A. Whyte, C. C. Kibbler, D. H. Ellis, M. C. J. Maiden, D. J. Shaw, and N. A. R. Gow (2006)
J. Clin. Microbiol. 44, 3647-3658
   Abstract »    Full Text »    PDF »
Hypermutable bacteria isolated from humans - a critical analysis..
L. M. C. Hall and S. K. Henderson-Begg (2006)
Microbiology 152, 2505-2514
   Abstract »    Full Text »    PDF »
Ecological Advantages of Autolysis during the Development and Dispersal of Pseudoalteromonas tunicata Biofilms.
A. Mai-Prochnow, J. S. Webb, B. C. Ferrari, and S. Kjelleberg (2006)
Appl. Envir. Microbiol. 72, 5414-5420
   Abstract »    Full Text »    PDF »
Expression and antimicrobial function of bactericidal permeability-increasing protein in cystic fibrosis patients..
D. Aichele, M. Schnare, M. Saake, M. Rollinghoff, and A. Gessner (2006)
Infect. Immun. 74, 4708-4714
   Abstract »    Full Text »    PDF »
Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy.
D. F. Warner and V. Mizrahi (2006)
Clin. Microbiol. Rev. 19, 558-570
   Abstract »    Full Text »    PDF »
From the Cover: Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients.
E. E. Smith, D. G. Buckley, Z. Wu, C. Saenphimmachak, L. R. Hoffman, D. A. D'Argenio, S. I. Miller, B. W. Ramsey, D. P. Speert, S. M. Moskowitz, et al. (2006)
PNAS 103, 8487-8492
   Abstract »    Full Text »    PDF »
Stepwise Upregulation of the Pseudomonas aeruginosa Chromosomal Cephalosporinase Conferring High-Level {beta}-Lactam Resistance Involves Three AmpD Homologues..
C. Juan, B. Moya, J. L. Perez, and A. Oliver (2006)
Antimicrob. Agents Chemother. 50, 1780-1787
   Abstract »    Full Text »    PDF »
Airway Mucus: From Production to Secretion.
O. W. Williams, A. Sharafkhaneh, V. Kim, B. F. Dickey, and C. M. Evans (2006)
Am. J. Respir. Cell Mol. Biol. 34, 527-536
   Abstract »    Full Text »    PDF »
Efficacy and Potential for Resistance Selection of Antipseudomonal Treatments in a Mouse Model of Lung Infection by Hypermutable Pseudomonas aeruginosa.
M. D. Macia, N. Borrell, M. Segura, C. Gomez, J. L. Perez, and A. Oliver (2006)
Antimicrob. Agents Chemother. 50, 975-983
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa inhibits endocytic recycling of CFTR in polarized human airway epithelial cells.
A. Swiatecka-Urban, S. Moreau-Marquis, D. P. MacEachran, J. P. Connolly, C. R. Stanton, J. R. Su, R. Barnaby, G. A. O'Toole, and B. A. Stanton (2006)
Am J Physiol Cell Physiol 290, C862-C872
   Abstract »    Full Text »    PDF »
Experimental evolution of resistance to an antimicrobial peptide.
G. G Perron, M. Zasloff, and G. Bell (2006)
Proc R Soc B 273, 251-256
   Abstract »    Full Text »    PDF »
Induction and Inhibition of Ciprofloxacin Resistance-Conferring Mutations in Hypermutator Bacteria.
R. T. Cirz and F. E. Romesberg (2006)
Antimicrob. Agents Chemother. 50, 220-225
   Abstract »    Full Text »    PDF »
Escherichia coli mutators: selection criteria and migration effect.
L. Le Chat, M. Fons, and F. Taddei (2006)
Microbiology 152, 67-73
   Abstract »    Full Text »    PDF »
The Evolution of Mutation Rate in Finite Asexual Populations.
J.-B. Andre and B. Godelle (2006)
Genetics 172, 611-626
   Abstract »    Full Text »    PDF »
Discovery and Characterization of the Cryptic {Psi} Subunit of the Pseudomonad DNA Replicase.
T. C. Jarvis, A. A. Beaudry, J. M. Bullard, U. Ochsner, H. G. Dallmann, and C. S. McHenry (2005)
J. Biol. Chem. 280, 40465-40473
   Abstract »    Full Text »    PDF »
Pathogenesis of Early Lung Disease in Cystic Fibrosis: A Window of Opportunity To Eradicate Bacteria.
T. D. Starner and P. B. McCray Jr. (2005)
Ann Intern Med 143, 816-822
   Full Text »    PDF »
Adaptations of Pseudomonas aeruginosa to the Cystic Fibrosis Lung Environment Can Include Deregulation of zwf, Encoding Glucose-6-Phosphate Dehydrogenase.
L. Silo-Suh, S.-J. Suh, P. V. Phibbs, and D. E. Ohman (2005)
J. Bacteriol. 187, 7561-7568
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa AmpR Is a Global Transcriptional Factor That Regulates Expression of AmpC and PoxB {beta}-Lactamases, Proteases, Quorum Sensing, and Other Virulence Factors.
K.-F. Kong, S. R. Jayawardena, S. D. Indulkar, A. del Puerto, C.-L. Koh, N. Hoiby, and K. Mathee (2005)
Antimicrob. Agents Chemother. 49, 4567-4575
   Abstract »    Full Text »    PDF »
Molecular Mechanisms of {beta}-Lactam Resistance Mediated by AmpC Hyperproduction in Pseudomonas aeruginosa Clinical Strains.
C. Juan, M. D. Macia, O. Gutierrez, C. Vidal, J. L. Perez, and A. Oliver (2005)
Antimicrob. Agents Chemother. 49, 4733-4738
   Abstract »    Full Text »    PDF »
Increased Mutation Frequencies in Escherichia coli Isolates Harboring Extended-Spectrum {beta}-Lactamases.
M.-R. Baquero, J. C. Galan, M. del Carmen Turrientes, R. Canton, T. M. Coque, J. L. Martinez, and F. Baquero (2005)
Antimicrob. Agents Chemother. 49, 4754-4756
   Abstract »    Full Text »    PDF »
Antibiotic Susceptibilities of Pseudomonas aeruginosa Isolates Derived from Patients with Cystic Fibrosis under Aerobic, Anaerobic, and Biofilm Conditions.
D. Hill, B. Rose, A. Pajkos, M. Robinson, P. Bye, S. Bell, M. Elkins, B. Thompson, C. MacLeod, S. D. Aaron, et al. (2005)
J. Clin. Microbiol. 43, 5085-5090
   Abstract »    Full Text »    PDF »
Intermediate Mutation Frequencies Favor Evolution of Multidrug Resistance in Escherichia coli.
E. Denamur, O. Tenaillon, C. Deschamps, D. Skurnik, E. Ronco, J. L. Gaillard, B. Picard, C. Branger, and I. Matic (2005)
Genetics 171, 825-827
   Abstract »    Full Text »    PDF »
Breakpoints for Predicting Pseudomonas aeruginosa Susceptibility to Inhaled Tobramycin in Cystic Fibrosis Patients: Use of High-Range Etest Strips.
M. I. Morosini, M. Garcia-Castillo, E. Loza, M. Perez-Vazquez, F. Baquero, and R. Canton (2005)
J. Clin. Microbiol. 43, 4480-4485
   Abstract »    Full Text »    PDF »
Hypermutation Is a Key Factor in Development of Multiple-Antimicrobial Resistance in Pseudomonas aeruginosa Strains Causing Chronic Lung Infections.
M. D. Macia, D. Blanquer, B. Togores, J. Sauleda, J. L. Perez, and A. Oliver (2005)
Antimicrob. Agents Chemother. 49, 3382-3386
   Abstract »    Full Text »    PDF »
Characterization of Colony Morphology Variants Isolated from Pseudomonas aeruginosa Biofilms.
M. J. Kirisits, L. Prost, M. Starkey, and M. R. Parsek (2005)
Appl. Envir. Microbiol. 71, 4809-4821
   Abstract »    Full Text »    PDF »
Effect of subinhibitory concentrations of ciprofloxacin on Mycobacterium fortuitum mutation rates.
S. H. Gillespie, S. Basu, A. L. Dickens, D. M. O'Sullivan, and T. D. McHugh (2005)
J. Antimicrob. Chemother. 56, 344-348
   Abstract »    Full Text »    PDF »
The effect of a bacteriophage on diversification of the opportunistic bacterial pathogen, Pseudomonas aeruginosa.
M. A Brockhurst, A. Buckling, and P. B Rainey (2005)
Proc R Soc B 272, 1385-1391
   Abstract »    Full Text »    PDF »
Occurrence of Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Patients Is Associated with the Oxidative Stress Caused by Chronic Lung Inflammation.
O. Ciofu, B. Riis, T. Pressler, H. E. Poulsen, and N. Hoiby (2005)
Antimicrob. Agents Chemother. 49, 2276-2282
   Abstract »    Full Text »    PDF »
Phenotypic variability of Pseudomonas aeruginosa in sputa from patients with acute infective exacerbation of cystic fibrosis and its impact on the validity of antimicrobial susceptibility testing.
J. E. Foweraker, C. R. Laughton, D. F. J. Brown, and D. Bilton (2005)
J. Antimicrob. Chemother. 55, 921-927
   Abstract »    Full Text »    PDF »
Hypermutable and Fluoroquinolone-Resistant Clinical Isolates of Staphylococcus aureus.
H. N. Trong, A.-L. Prunier, and R. Leclercq (2005)
Antimicrob. Agents Chemother. 49, 2098-2101
   Abstract »    Full Text »    PDF »
Population Structure, Antimicrobial Resistance, and Mutation Frequencies of Streptococcus pneumoniae Isolates from Cystic Fibrosis Patients.
R. del Campo, M.-I. Morosini, E. G.-G. de la Pedrosa, A. Fenoll, C. Munoz-Almagro, L. Maiz, F. Baquero, R. Canton, and the Spanish Pneumococcal Infection Study Network (2005)
J. Clin. Microbiol. 43, 2207-2214
   Abstract »    Full Text »    PDF »
Antimutator Role of DNA Glycosylase MutY in Pathogenic Neisseria Species.
T. Davidsen, M. Bjoras, E. C. Seeberg, and T. Tonjum (2005)
J. Bacteriol. 187, 2801-2809
   Abstract »    Full Text »    PDF »
Impact of mutS Inactivation on Foreign DNA Acquisition by Natural Transformation in Pseudomonas stutzeri.
P. Meier and W. Wackernagel (2005)
J. Bacteriol. 187, 143-154
   Abstract »    Full Text »    PDF »
Bacteriophage and Phenotypic Variation in Pseudomonas aeruginosa Biofilm Development.
J. S. Webb, M. Lau, and S. Kjelleberg (2004)
J. Bacteriol. 186, 8066-8073
   Abstract »    Full Text »    PDF »
Bile-Induced DNA Damage in Salmonella enterica.
A. I. Prieto, F. Ramos-Morales, and J. Casadesus (2004)
Genetics 168, 1787-1794
   Abstract »    Full Text »    PDF »
From the Cover: Self-generated diversity produces "insurance effects" in biofilm communities.
B. R. Boles, M. Thoendel, and P. K. Singh (2004)
PNAS 101, 16630-16635
   Abstract »    Full Text »    PDF »
Long-Term Effect of Mutagenic DNA Repair on Accumulation of Mutations in Pseudomonas syringae B86-17.
S. Zhang and G. W. Sundin (2004)
J. Bacteriol. 186, 7807-7810
   Abstract »    Full Text »    PDF »
Hypermutation and the Preexistence of Antibiotic-Resistant Pseudomonas aeruginosa Mutants: Implications for Susceptibility Testing and Treatment of Chronic Infections.
A. Oliver, B. R. Levin, C. Juan, F. Baquero, and J. Blazquez (2004)
Antimicrob. Agents Chemother. 48, 4226-4233
   Abstract »    Full Text »    PDF »
Type III Secretion Phenotypes of Pseudomonas aeruginosa Strains Change during Infection of Individuals with Cystic Fibrosis.
M. Jain, D. Ramirez, R. Seshadri, J. F. Cullina, C. A. Powers, G. S. Schulert, M. Bar-Meir, C. L. Sullivan, S. A. McColley, and A. R. Hauser (2004)
J. Clin. Microbiol. 42, 5229-5237
   Abstract »    Full Text »    PDF »
Experimental Adaptation of Salmonella typhimurium to Mice.
A. I. Nilsson, E. Kugelberg, O. G. Berg, and D. I. Andersson (2004)
Genetics 168, 1119-1130
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)