HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Montanari, S. Articles by Bragonzi, A. Search for Related Content PubMed PubMed Citation Articles by Montanari, S. Articles by Bragonzi, A. Agricola Articles by Montanari, S. Articles by Bragonzi, A.

Biological cost of hypermutation in Pseudomonas aeruginosa strains from patients with cystic fibrosis

¹ Institute for Experimental Treatment of Cystic Fibrosis, Scientific Institute H. S. Raffaele, Milano, Italy
² Servicio de Microbiologìa Hospital Son Dureta, Palma de Mallorca, Spain
³ Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Milano, Italy
⁴ Klinische Forschergruppe, OE 6710, Medizinische Hochschule Hannover, Hannover, Germany
⁵ Ospedale Maggiore Policlinico, CF Clinic, Milano, Italy
⁶ Institute of Medical Microbiology and Hygiene, Universitätsklinikum Tübingen, Tübingen, Germany

Correspondence
Alessandra Bragonzi
bragonzi.alessandra{at}hsr.it

The high prevalence of hypermutable (mismatch repair-deficient) Pseudomonas aeruginosa strains in patients with cystic fibrosis (CF) is thought to be driven by their co-selection with adaptive mutations required for long-term persistence. Whether the increased mutation rate of naturally hypermutable strains is associated with a biological benefit or cost for the colonization of secondary environments is not known. Thirty-nine P. aeruginosa strains were collected from ten patients with CF during their course of chronic lung infections and screened for hypermutability. Seven hypermutable P. aeruginosa strains (18 %) isolated from six patients with CF (60 %) were identified and assigned to five different genotypes. Complementation and sequence analysis in the mutS, mutL and uvrD genes of these hypermutable P. aeruginosa strains revealed novel mutations. To understand the consequences of hypermutation for the fitness of the organisms, five pairs of clinical wild-type/hypermutable, clonally related P. aeruginosa strains and the laboratory strains PAO1/PAO1mutS were subjected to competition in vitro and in the agar-beads mouse model of chronic airway infection. When tested in competition assay in vitro, the wild-type outcompeted four clinical hypermutable strains and the PAO1mutS strain. In vivo, all of the hypermutable strains were less efficient at establishing lung infection than their wild-type clones. These results suggest that P. aeruginosa hypermutation is associated with a biological cost, reducing the potential for colonization of new environments and therefore strain transmissibility.

This article has been cited by other articles:

				A. Bragonzi, M. Paroni, A. Nonis, N. Cramer, S. Montanari, J. Rejman, C. Di Serio, G. Doring, and B. Tummler Pseudomonas aeruginosa Microevolution during Cystic Fibrosis Lung Infection Establishes Clones with Adapted Virulence Am. J. Respir. Crit. Care Med., July 15, 2009; 180(2): 138 - 145. [Abstract] [Full Text] [PDF]

				L. F. Mandsberg, O. Ciofu, N. Kirkby, L. E. Christiansen, H. E. Poulsen, and N. Hoiby Antibiotic Resistance in Pseudomonas aeruginosa Strains with Increased Mutation Frequency Due to Inactivation of the DNA Oxidative Repair System Antimicrob. Agents Chemother., June 1, 2009; 53(6): 2483 - 2491. [Abstract] [Full Text] [PDF]

				A. Mena, E. E. Smith, J. L. Burns, D. P. Speert, S. M. Moskowitz, J. L. Perez, and A. Oliver Genetic Adaptation of Pseudomonas aeruginosa to the Airways of Cystic Fibrosis Patients Is Catalyzed by Hypermutation J. Bacteriol., December 15, 2008; 190(24): 7910 - 7917. [Abstract] [Full Text] [PDF]

				I. Wiegand, A. K. Marr, E. B. M. Breidenstein, K. N. Schurek, P. Taylor, and R. E. W. Hancock Mutator Genes Giving Rise to Decreased Antibiotic Susceptibility in Pseudomonas aeruginosa Antimicrob. Agents Chemother., October 1, 2008; 52(10): 3810 - 3813. [Abstract] [Full Text] [PDF]

				S. Besier, J. Zander, B. C. Kahl, P. Kraiczy, V. Brade, and T. A. Wichelhaus The Thymidine-Dependent Small-Colony-Variant Phenotype Is Associated with Hypermutability and Antibiotic Resistance in Clinical Staphylococcus aureus Isolates Antimicrob. Agents Chemother., June 1, 2008; 52(6): 2183 - 2189. [Abstract] [Full Text] [PDF]

				M. D. Macia, A. Mena, N. Borrell, J. L. Perez, and A. Oliver Increased Susceptibility to Colistin in Hypermutable Pseudomonas aeruginosa Strains from Chronic Respiratory Infections Antimicrob. Agents Chemother., December 1, 2007; 51(12): 4531 - 4532. [Full Text] [PDF]

				S. M. Kirov, J. S. Webb, C. Y. O'May, D. W. Reid, J. K. K. Woo, S. A. Rice, and S. Kjelleberg Biofilm differentiation and dispersal in mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis Microbiology, October 1, 2007; 153(10): 3264 - 3274. [Abstract] [Full Text] [PDF]