Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs

Peter Jorth; Benjamin J Staudinger; Xia Wu; Katherine B Hisert; Hillary Hayden; Jayanthi Garudathri; Christopher L Harding; Matthew C Radey; Amir Rezayat; Gilbert Bautista; William R Berrington; Amanda F Goddard; Chunxiang Zheng; Angus Angermeyer; Mitchell J Brittnacher; Jacob Kitzman; Jay Shendure; Corinne L Fligner; John Mittler; Moira L Aitken; Colin Manoil; James E Bruce; Timothy L Yahr; Pradeep K Singh

doi:10.1016/j.chom.2015.07.006

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Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs

Journal article

Open access

Peer reviewed

Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs

Peter Jorth, Benjamin J Staudinger, Xia Wu, Katherine B Hisert, Hillary Hayden, Jayanthi Garudathri, Christopher L Harding, Matthew C Radey, Amir Rezayat, Gilbert Bautista, …

Cell host & microbe, Vol.18(3), pp.307-319

09/09/2015

DOI: 10.1016/j.chom.2015.07.006

PMCID: PMC4589543

PMID: 26299432

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Abstract

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 ∼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.

Genetic Variation

Lung - microbiology

Pseudomonas aeruginosa - isolation & purification

Pseudomonas aeruginosa - genetics

Humans

Molecular Sequence Data

Cystic Fibrosis - complications

Pseudomonas aeruginosa - classification

Pseudomonas Infections - microbiology

Sequence Analysis, DNA

Details

Title: Subtitle: Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs
Creators: Peter Jorth - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Benjamin J Staudinger - Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
Xia Wu - Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Katherine B Hisert - Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
Hillary Hayden - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Jayanthi Garudathri - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Christopher L Harding - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Matthew C Radey - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Amir Rezayat - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Gilbert Bautista - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
William R Berrington - Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
Amanda F Goddard - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Chunxiang Zheng - Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Angus Angermeyer - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Mitchell J Brittnacher - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Jacob Kitzman - Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Jay Shendure - Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Corinne L Fligner - Departments of Pathology and Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
John Mittler - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA
Moira L Aitken - Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
Colin Manoil - Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
James E Bruce - Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Timothy L Yahr - Department of Microbiology, University of Iowa School of Medicine, Iowa City, IA 52240, USA
Pradeep K Singh - Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: singhpr@u.washington.edu
Resource Type: Journal article
Publication Details: Cell host & microbe, Vol.18(3), pp.307-319
Publisher: United States
DOI: 10.1016/j.chom.2015.07.006
PMID: 26299432
PMCID: PMC4589543
ISSN: 1931-3128
eISSN: 1934-6069
Grant note: K24 HL102246 / NHLBI NIH HHS R01 HL075784 / NHLBI NIH HHS P30 DK089507 / NIDDK NIH HHS R01 AI101307 / NIAID NIH HHS K24HL102246 / NHLBI NIH HHS P30DK089507 / NIDDK NIH HHS P30 DK054759 / NIDDK NIH HHS R01AI101307 / NIAID NIH HHS R01HL110879 / NHLBI NIH HHS
Language: English
Date published: 09/09/2015
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001141902771

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