Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung
Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these infections are well studied, we know little about the short-term population dynamics that enable this pathog...
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| Format: | Online |
| Language: | English |
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American Society of Microbiology
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556809/ |
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pubmed-4556809 |
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pubmed-45568092015-09-04 Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung Diaz Caballero, Julio Clark, Shawn T. Coburn, Bryan Zhang, Yu Wang, Pauline W. Donaldson, Sylva L. Tullis, D. Elizabeth Yau, Yvonne C. W. Waters, Valerie J. Hwang, David M. Guttman, David S. Research Article Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these infections are well studied, we know little about the short-term population dynamics that enable this pathogen to persist despite aggressive antimicrobial therapy. Here, we describe a short-term population genomic analysis of 233 P. aeruginosa isolates collected from 12 sputum specimens obtained over a 1-year period from a single patient. Whole-genome sequencing and antimicrobial susceptibility profiling identified the expansion of two clonal lineages. The first lineage originated from the coalescence of the entire sample less than 3 years before the end of the study and gave rise to a high-diversity ancestral population. The second expansion occurred 2 years later and gave rise to a derived population with a strong signal of positive selection. These events show characteristics consistent with recurrent selective sweeps. While we cannot identify the specific mutations responsible for the origins of the clonal lineages, we find that the majority of mutations occur in loci previously associated with virulence and resistance. Additionally, approximately one-third of all mutations occur in loci that are mutated multiple times, highlighting the importance of parallel pathoadaptation. One such locus is the gene encoding penicillin-binding protein 3, which received three independent mutations. Our functional analysis of these alleles shows that they provide differential fitness benefits dependent on the antibiotic under selection. These data reveal that bacterial populations can undergo extensive and dramatic changes that are not revealed by lower-resolution analyses. American Society of Microbiology 2015-09-01 /pmc/articles/PMC4556809/ /pubmed/26330513 http://dx.doi.org/10.1128/mBio.00981-15 Text en Copyright © 2015 Diaz Caballero et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Diaz Caballero, Julio Clark, Shawn T. Coburn, Bryan Zhang, Yu Wang, Pauline W. Donaldson, Sylva L. Tullis, D. Elizabeth Yau, Yvonne C. W. Waters, Valerie J. Hwang, David M. Guttman, David S. |
| spellingShingle |
Diaz Caballero, Julio Clark, Shawn T. Coburn, Bryan Zhang, Yu Wang, Pauline W. Donaldson, Sylva L. Tullis, D. Elizabeth Yau, Yvonne C. W. Waters, Valerie J. Hwang, David M. Guttman, David S. Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung |
| author_facet |
Diaz Caballero, Julio Clark, Shawn T. Coburn, Bryan Zhang, Yu Wang, Pauline W. Donaldson, Sylva L. Tullis, D. Elizabeth Yau, Yvonne C. W. Waters, Valerie J. Hwang, David M. Guttman, David S. |
| author_sort |
Diaz Caballero, Julio |
| title |
Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung |
| title_short |
Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung |
| title_full |
Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung |
| title_fullStr |
Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung |
| title_full_unstemmed |
Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung |
| title_sort |
selective sweeps and parallel pathoadaptation drive pseudomonas aeruginosa evolution in the cystic fibrosis lung |
| description |
Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these infections are well studied, we know little about the short-term population dynamics that enable this pathogen to persist despite aggressive antimicrobial therapy. Here, we describe a short-term population genomic analysis of 233 P. aeruginosa isolates collected from 12 sputum specimens obtained over a 1-year period from a single patient. Whole-genome sequencing and antimicrobial susceptibility profiling identified the expansion of two clonal lineages. The first lineage originated from the coalescence of the entire sample less than 3 years before the end of the study and gave rise to a high-diversity ancestral population. The second expansion occurred 2 years later and gave rise to a derived population with a strong signal of positive selection. These events show characteristics consistent with recurrent selective sweeps. While we cannot identify the specific mutations responsible for the origins of the clonal lineages, we find that the majority of mutations occur in loci previously associated with virulence and resistance. Additionally, approximately one-third of all mutations occur in loci that are mutated multiple times, highlighting the importance of parallel pathoadaptation. One such locus is the gene encoding penicillin-binding protein 3, which received three independent mutations. Our functional analysis of these alleles shows that they provide differential fitness benefits dependent on the antibiotic under selection. These data reveal that bacterial populations can undergo extensive and dramatic changes that are not revealed by lower-resolution analyses. |
| publisher |
American Society of Microbiology |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556809/ |
| _version_ |
1613471689290547200 |