ArticleNature genetics2014
Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures.
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers.
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Who cites it
186 citing papers in PubMed, 291 citations in OpenAlex.
- Trial
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- De novo mutations mediate phenotypic switching in an opportunistic human lung pathogen.Nature communications · 2025Article
- Antimicrobial Agent Trimethoprim Influences Chemical Interactions in Cystic Fibrosis Pathogens via theACS chemical biology · 2025Article
- Population sequencing for phylogenetic diversity and transmission analyses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
126 more citing papers are in PubMed but not listed here.
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7 authors at 3 institutions in 2 countries.
Funding
Abstract
Advances in sequencing technologies have enabled the identification of mutations acquired by bacterial pathogens during infection. However, it remains unclear whether adaptive mutations fix in the population or lead to pathogen diversification within the patient. Here we study the genotypic diversity of Burkholderia dolosa within individuals with cystic fibrosis by resequencing individual colonies and whole populations from single sputum samples. We find extensive intrasample diversity, suggesting that mutations rarely fix in a patient's pathogen population--instead, diversifying lineages coexist for many years. Under strong selection, multiple adaptive mutations arise, but none of these sweep 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 the selective pressures acting on a pathogen in individual patients based on single clinical samples.
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