دورية أكاديمية
Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs.
| العنوان: | Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs. |
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| المؤلفون: | Lee AH; Department of Microbiology and Immunology.; Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada., Flibotte S; Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.; Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada., Sinha S; Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada., Paiero A; Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada., Ehrlich RL; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.; Genomics Core Facility, Clinical and Translational Research Institute, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.; Center for Genomic Sciences, Institute for Molecular Medicine and Infection Diseases, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA., Balashov S; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.; Genomics Core Facility, Clinical and Translational Research Institute, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.; Center for Genomic Sciences, Institute for Molecular Medicine and Infection Diseases, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA., Ehrlich GD; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.; Genomics Core Facility, Clinical and Translational Research Institute, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.; Center for Genomic Sciences, Institute for Molecular Medicine and Infection Diseases, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA., Zlosnik JE; Centre for Preventing and Understanding Infection in Children, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada., Mell JC; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.; Genomics Core Facility, Clinical and Translational Research Institute, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.; Center for Genomic Sciences, Institute for Molecular Medicine and Infection Diseases, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA., Nislow C; Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. |
| المصدر: | Genome research [Genome Res] 2017 Apr; Vol. 27 (4), pp. 650-662. Date of Electronic Publication: 2017 Mar 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9518021 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-5469 (Electronic) Linking ISSN: 10889051 NLM ISO Abbreviation: Genome Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press, c1995- |
| مواضيع طبية MeSH: | Phenotype* , Polymorphism, Genetic*, Burkholderia Infections/*microbiology , Burkholderia cenocepacia/*genetics , Cystic Fibrosis/*microbiology, Adolescent ; Animals ; Biofilms ; Burkholderia Infections/complications ; Burkholderia cenocepacia/isolation & purification ; Burkholderia cenocepacia/pathogenicity ; Burkholderia cenocepacia/physiology ; Child ; Child, Preschool ; Cystic Fibrosis/complications ; Genotype ; Humans ; Lung/microbiology ; Moths/microbiology ; Virulence ; Young Adult |
| مستخلص: | 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. (© 2017 Lee et al.; Published by Cold Spring Harbor Laboratory Press.) |
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| معلومات مُعتمدة: | R01 DC002148 United States DC NIDCD NIH HHS |
| تواريخ الأحداث: | Date Created: 20170323 Date Completed: 20180112 Latest Revision: 20181113 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5378182 |
| DOI: | 10.1101/gr.213363.116 |
| PMID: | 28325850 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1549-5469 |
|---|---|
| DOI: | 10.1101/gr.213363.116 |