Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients

被引:1031
作者
Smith, Eric E.
Buckley, Danielle G.
Wu, Zaining
Saenphimmachak, Channakhone
Hoffman, Lucas R.
D'Argenio, David A.
Miller, Samuel I.
Ramsey, Bonnie W.
Speert, David P.
Moskowitz, Samuel M.
Burns, Jane L.
Kaul, Rajinder
Olson, Maynard V.
机构
[1] Univ Washington, Genome Ctr, Seattle, WA 98195 USA
[2] Univ Washington, Program Mol & Cellular Biol, Seattle, WA 98195 USA
[3] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA
[4] Univ Washington, Dept Pediat, Seattle, WA 98195 USA
[5] Univ Washington, Dept Med, Seattle, WA 98195 USA
[6] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[7] British Columbia Res Inst Childrens & Womens Hlth, Dept Pediat, Div Infect Dis & Immunol, Vancouver, BC V5Z 4H4, Canada
关键词
chronic infection; positive selection; virulence; antibiotic resistance;
D O I
10.1073/pnas.0602138103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 CIF 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 A 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.
引用
收藏
页码:8487 / 8492
页数:6
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