Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs

被引：224

作者：

Jorth, Peter ^{[1
]}

Staudinger, Benjamin J. ^{[2
]}

Wu, Xia ^{[3
]}

Hisert, Katherine B. ^{[2
]}

Hayden, Hillary ^{[1
]}

Garudathri, Jayanthi ^{[1
]}

Harding, Christopher L. ^{[1
]}

Radey, Matthew C. ^{[1
]}

Rezayat, Amir ^{[1
]}

Bautista, Gilbert ^{[1
]}

Berrington, William R. ^{[2
]}

Goddard, Amanda F. ^{[1
]}

Zheng, Chunxiang ^{[3
]}

Angermeyer, Angus ^{[1
]}

Brittnacher, Mitchell J. ^{[1
]}

Kitzman, Jacob ^{[3
]}

Shendure, Jay ^{[3
]}

Fligner, Corinne L. ^{[4
,5
]}

Mittler, John ^{[1
]}

Aitken, Moira L. ^{[2
]}

Manoil, Colin ^{[3
]}

Bruce, James E. ^{[3
]}

Yahr, Timothy L. ^{[6
]}

Singh, Pradeep K. ^{[1
,2
]}

机构：

[1] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA

[2] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA

[3] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA

[4] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA

[5] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA

[6] Univ Iowa, Sch Med, Dept Microbiol, Iowa City, IA 52240 USA

来源：

CELL HOST & MICROBE | 2015年 / 18卷 / 03期

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; PSEUDOMONAS-AERUGINOSA; III SECRETION; ADAPTIVE RADIATION; YOUNG-CHILDREN; EVOLUTION; DIVERSITY; GENOME; COMPARTMENTALIZATION; POPULATIONS;

D O I：

10.1016/j.chom.2015.07.006

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Bacterial lineages that chronically infect cystic fibrosis (CF) patients genetically diversify during infection. However, the mechanisms driving diversification are unknown. By dissecting ten CF lung pairs and studying similar to 12,000 regional isolates, we were able to investigate whether clonally related Pseudomonas aeruginosa inhabiting different lung regions evolve independently and differ functionally. Phylogenetic analysis of genome sequences showed that regional isolation of P. aeruginosa drives divergent evolution. We investigated the consequences of regional evolution by studying isolates from mildly and severely diseased lung regions and found evolved differences in bacterial nutritional requirements, host defense and antibiotic resistance, and virulence due to hyperactivity of the type 3 secretion system. These findings suggest that bacterial intermixing is limited in CF lungs and that regional selective pressures may markedly differ. The findings also may explain how specialized bacterial variants arise during infection and raise the possibility that pathogen diversification occurs in other chronic infections characterized by spatially heterogeneous conditions.

引用

页码：307 / 319

页数：13

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