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Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs
Chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. Tracking bacterial evolution during chronic infections can provide insights into how host selection pressures—including immune responses and therapeutic interventions—shape bacteria...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378182/ https://www.ncbi.nlm.nih.gov/pubmed/28325850 http://dx.doi.org/10.1101/gr.213363.116 |
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author | Lee, Amy Huei-Yi Flibotte, Stephane Sinha, Sunita Paiero, Adrianna Ehrlich, Rachel L. Balashov, Sergey Ehrlich, Garth D. Zlosnik, James E.A. Mell, Joshua Chang Nislow, Corey |
author_facet | Lee, Amy Huei-Yi Flibotte, Stephane Sinha, Sunita Paiero, Adrianna Ehrlich, Rachel L. Balashov, Sergey Ehrlich, Garth D. Zlosnik, James E.A. Mell, Joshua Chang Nislow, Corey |
author_sort | Lee, Amy Huei-Yi |
collection | PubMed |
description | Chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. Tracking bacterial evolution during chronic infections can provide insights into how host selection pressures—including immune responses and therapeutic interventions—shape bacterial genomes. We carried out genomic and phenotypic analyses of 215 serially collected Burkholderia cenocepacia isolates from 16 cystic fibrosis patients, spanning a period of 2–20 yr and a broad range of epidemic lineages. Systematic phenotypic tests identified longitudinal bacterial series that manifested progressive changes in liquid media growth, motility, biofilm formation, and acute insect virulence, but not in mucoidy. The results suggest that distinct lineages follow distinct evolutionary trajectories during lung infection. Pan-genome analysis identified 10,110 homologous gene clusters present only in a subset of strains, including genes restricted to different molecular types. Our phylogenetic analysis based on 2148 orthologous gene clusters from all isolates is consistent with patient-specific clades. This suggests that initial colonization of patients was likely by individual strains, followed by subsequent diversification. Evidence of clonal lineages shared by some patients was observed, suggesting inter-patient transmission. We observed recurrent gene losses in multiple independent longitudinal series, including complete loss of Chromosome III and deletions on other chromosomes. Recurrently observed loss-of-function mutations were associated with decreases in motility and biofilm formation. Together, our study provides the first comprehensive genome-phenome analyses of B. cenocepacia infection in cystic fibrosis lungs and serves as a valuable resource for understanding the genomic and phenotypic underpinnings of bacterial evolution. |
format | Online Article Text |
id | pubmed-5378182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53781822017-04-12 Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs Lee, Amy Huei-Yi Flibotte, Stephane Sinha, Sunita Paiero, Adrianna Ehrlich, Rachel L. Balashov, Sergey Ehrlich, Garth D. Zlosnik, James E.A. Mell, Joshua Chang Nislow, Corey Genome Res Resource Chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. Tracking bacterial evolution during chronic infections can provide insights into how host selection pressures—including immune responses and therapeutic interventions—shape bacterial genomes. We carried out genomic and phenotypic analyses of 215 serially collected Burkholderia cenocepacia isolates from 16 cystic fibrosis patients, spanning a period of 2–20 yr and a broad range of epidemic lineages. Systematic phenotypic tests identified longitudinal bacterial series that manifested progressive changes in liquid media growth, motility, biofilm formation, and acute insect virulence, but not in mucoidy. The results suggest that distinct lineages follow distinct evolutionary trajectories during lung infection. Pan-genome analysis identified 10,110 homologous gene clusters present only in a subset of strains, including genes restricted to different molecular types. Our phylogenetic analysis based on 2148 orthologous gene clusters from all isolates is consistent with patient-specific clades. This suggests that initial colonization of patients was likely by individual strains, followed by subsequent diversification. Evidence of clonal lineages shared by some patients was observed, suggesting inter-patient transmission. We observed recurrent gene losses in multiple independent longitudinal series, including complete loss of Chromosome III and deletions on other chromosomes. Recurrently observed loss-of-function mutations were associated with decreases in motility and biofilm formation. Together, our study provides the first comprehensive genome-phenome analyses of B. cenocepacia infection in cystic fibrosis lungs and serves as a valuable resource for understanding the genomic and phenotypic underpinnings of bacterial evolution. Cold Spring Harbor Laboratory Press 2017-04 /pmc/articles/PMC5378182/ /pubmed/28325850 http://dx.doi.org/10.1101/gr.213363.116 Text en © 2017 Lee et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Resource Lee, Amy Huei-Yi Flibotte, Stephane Sinha, Sunita Paiero, Adrianna Ehrlich, Rachel L. Balashov, Sergey Ehrlich, Garth D. Zlosnik, James E.A. Mell, Joshua Chang Nislow, Corey Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs |
title | Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs |
title_full | Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs |
title_fullStr | Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs |
title_full_unstemmed | Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs |
title_short | Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs |
title_sort | phenotypic diversity and genotypic flexibility of burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs |
topic | Resource |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378182/ https://www.ncbi.nlm.nih.gov/pubmed/28325850 http://dx.doi.org/10.1101/gr.213363.116 |
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