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Published online on May 10, 2006, 10.1073/pnas.0602138103
PNAS | May 30, 2006 | vol. 103 | no. 22 | 8487-8492


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From the Cover
BIOLOGICAL SCIENCES / MICROBIOLOGY
Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients

Eric E. Smith*,{dagger}, Danielle G. Buckley{ddagger}, Zaining Wu{ddagger}, Channakhone Saenphimmachak{ddagger}, Lucas R. Hoffman§, David A. D’Argenio, Samuel I. Miller,||, Bonnie W. Ramsey§, David P. Speert**, Samuel M. Moskowitz§, Jane L. Burns§, Rajinder Kaul{ddagger},{dagger}{dagger}, and Maynard V. Olson{ddagger},||,{dagger}{dagger},{ddagger}{ddagger}

{ddagger}Genome Center, *Program in Molecular and Cellular Biology, and Departments of Microbiology, §Pediatrics, {dagger}{dagger}Medicine, and ||Genome Sciences, University of Washington, Seattle, WA 98195; and **Division of Infectious and Immunological Diseases, Department of Pediatrics, British Columbia Research Institute for Children’s and Women’s Health, 950 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4

Contributed by Maynard V. Olson, March 20, 2006

In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa. The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the P. aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.

chronic infection | positive selection | virulence | antibiotic resistance

See Commentary on page 8305.

Author contributions: E.E.S. and M.V.O. designed research; E.E.S., D.G.B., Z.W., C.S., L.R.H., D.A.D., and R.K. performed research; S.I.M., B.W.R., D.P.S., S.M.M., and J.L.B. contributed new reagents/analytic tools; E.E.S. analyzed data; and E.E.S. wrote the paper.

Conflict of interest statement: No conflicts declared.

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. DQ470842).

{dagger}To whom correspondence may be addressed at: University of Washington, 1959 Northeast Pacific Street, Box 357730, Seattle, WA 98195. E-mail: smithee{at}u.washington.edu

{ddagger}{ddagger}To whom correspondence may be addressed at: University of Washington, Fluke Hall 316, Box 352145, Seattle, WA 98195. E-mail: mvo{at}u.washington.edu

© 2006 by The National Academy of Sciences of the USA


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Evolving stealth: Genetic adaptation of Pseudomonas aeruginosa during cystic fibrosis infections
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PNAS 2006 103: 8305-8306. [Extract] [Full Text]  



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