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Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures
Advances in sequencing have enabled the identification of mutations acquired by bacterial pathogens during infection(1-10). However, it remains unclear whether adaptive mutations fix in the population or lead to pathogen diversification within the patient(11,12). Here, we study the genotypic diversi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979468/ https://www.ncbi.nlm.nih.gov/pubmed/24316980 http://dx.doi.org/10.1038/ng.2848 |
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author | Lieberman, Tami D. Flett, Kelly B. Yelin, Idan Martin, Thomas R. McAdam, Alexander J. Priebe, Gregory P. Kishony, Roy |
author_facet | Lieberman, Tami D. Flett, Kelly B. Yelin, Idan Martin, Thomas R. McAdam, Alexander J. Priebe, Gregory P. Kishony, Roy |
author_sort | Lieberman, Tami D. |
collection | PubMed |
description | Advances in sequencing have enabled the identification of mutations acquired by bacterial pathogens during infection(1-10). However, it remains unclear whether adaptive mutations fix in the population or lead to pathogen diversification within the patient(11,12). Here, we study the genotypic diversity of Burkholderia dolosa within people with cystic fibrosis by re-sequencing individual colonies and whole populations from single sputum samples. Extensive intra-sample diversity reveals that mutations rarely fix within a patient's pathogen population—instead, diversifying lineages coexist for many years. When strong selection is acting on a gene, multiple adaptive mutations arise but neither sweeps to fixation, generating lasting allele diversity that provides a recorded signature of past selection. Genes involved in outer-membrane components, iron scavenging and antibiotic resistance all showed this signature of within-patient selection. These results offer a general and rapid approach for identifying selective pressures acting on a pathogen in individual patients based on single clinical samples. |
format | Online Article Text |
id | pubmed-3979468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-39794682014-07-01 Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures Lieberman, Tami D. Flett, Kelly B. Yelin, Idan Martin, Thomas R. McAdam, Alexander J. Priebe, Gregory P. Kishony, Roy Nat Genet Article Advances in sequencing have enabled the identification of mutations acquired by bacterial pathogens during infection(1-10). However, it remains unclear whether adaptive mutations fix in the population or lead to pathogen diversification within the patient(11,12). Here, we study the genotypic diversity of Burkholderia dolosa within people with cystic fibrosis by re-sequencing individual colonies and whole populations from single sputum samples. Extensive intra-sample diversity reveals that mutations rarely fix within a patient's pathogen population—instead, diversifying lineages coexist for many years. When strong selection is acting on a gene, multiple adaptive mutations arise but neither sweeps to fixation, generating lasting allele diversity that provides a recorded signature of past selection. Genes involved in outer-membrane components, iron scavenging and antibiotic resistance all showed this signature of within-patient selection. These results offer a general and rapid approach for identifying selective pressures acting on a pathogen in individual patients based on single clinical samples. 2013-12-08 2014-01 /pmc/articles/PMC3979468/ /pubmed/24316980 http://dx.doi.org/10.1038/ng.2848 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Lieberman, Tami D. Flett, Kelly B. Yelin, Idan Martin, Thomas R. McAdam, Alexander J. Priebe, Gregory P. Kishony, Roy Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures |
title | Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures |
title_full | Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures |
title_fullStr | Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures |
title_full_unstemmed | Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures |
title_short | Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures |
title_sort | genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979468/ https://www.ncbi.nlm.nih.gov/pubmed/24316980 http://dx.doi.org/10.1038/ng.2848 |
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