Phenotypic diversity and genotypic flexibility ofBurkholderia cenocepaciaduring 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 bacterial genomes. We carried out genomic and phenotypic analyses of 215 serially collectedBurkholderia cenocepaciaisolates 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 ofB. cenocepaciainfection in cystic fibrosis lungs and serves as a valuable resource for understanding the genomic and phenotypic underpinnings of bacterial evolution.
Department of Microbiology and Immunology.|Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Amy Huei-Yi
0000-0003-3250-3246
AH
Lee
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.
Stephane
S
Flibotte
Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Sunita
S
Sinha
Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Adrianna
A
Paiero
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.
Rachel L
RL
Ehrlich
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.
Sergey
S
Balashov
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.
Garth D
GD
Ehrlich
Centre for Preventing and Understanding Infection in Children, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
James E A
0000-0002-9708-9034
JE
Zlosnik
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.
Joshua Chang
0000-0003-0222-5636
JC
Mell
Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Corey
0000-0002-4016-8874
C
Nislow
D000293:Adolescent; D000818:Animals; D018441:Biofilms; D019121:Burkholderia Infections / Q000150:complications / Q000382:microbiology*; D057508:Burkholderia cenocepacia / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D005838:Genotype; D006801:Humans; D008168:Lung / Q000382:microbiology; D009036:Moths / Q000382:microbiology; D010641:Phenotype; D011110:Polymorphism, Genetic; D014774:Virulence; D055815:Young Adult