Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients.
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.
Smith
Eric E
EE
Genome Center, Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA. smithee@u.washington.edu
Buckley
Danielle G
DG
Wu
Zaining
Z
Saenphimmachak
Channakhone
C
Hoffman
Lucas R
LR
D'Argenio
David A
DA
Miller
Samuel I
SI
Ramsey
Bonnie W
BW
Speert
David P
DP
Moskowitz
Samuel M
SM
Burns
Jane L
JL
Kaul
Rajinder
R
Olson
Maynard V
MV