Advanced search
1 file | 3.82 MB Add to list

Genomics of an endemic cystic fibrosis Burkholderia multivorans strain reveals low within-patient evolution but high between-patient diversity

(2021) PLOS PATHOGENS. 17(3).
Author
Organization
Abstract
In many countries, Burkholderia multivorans is the most prevalent species within the Burkholderia cepacia complex (Bcc) found infecting the lungs of patients with cystic fibrosis (CF). Its positive identification is of immediate concern to the health of the patient as it is notoriously hard to eradicate using antibiotics and can cause necrosis of the lung tissues (cepacia syndrome). Infection control measures reduced the prevalence of B. cenocepacia in CF wards, but patients continue to acquire infections by B. multivorans from environmental sources. In most reported cases, the infecting strains are unique except in rare cases in which cross-infection is observed between patients. We report here an endemic strain of B. multivorans with sequence type ST-742 that has been infecting multiple patients, without evidence for cross-infection. We investigated the epidemiology and genomics of this ST-742 strain and show that it is microdiverse, as isolates between-patients exhibit numerous genomic differences, at scales that have not been observed previously when looking at evolutionary trajectories within-patients. Additionally, we found that the specific genomic background of a given strain may dictate the strategy of adaptation within the CF lung. Burkholderia multivorans is a member of the Burkholderia cepacia complex (Bcc), notorious for its pathogenicity in persons with cystic fibrosis. Epidemiological surveillance suggests that patients predominantly acquire B. multivorans from environmental sources, with rare cases of patient-to-patient transmission. Here we report on the genomic analysis of thirteen isolates from an endemic B. multivorans strain infecting four cystic fibrosis patients treated in different pediatric cystic fibrosis centers in Belgium, with no evidence of cross-infection. All isolates share an identical sequence type (ST-742) but whole genome analysis shows that they exhibit peculiar patterns of genomic diversity between patients. By combining short and long reads sequencing technologies, we highlight key differences in terms of small nucleotide polymorphisms indicative of low rates of adaptive evolution within patient, and well-defined, hundred Kbps-long segments of high enrichment in mutations between patients. In addition, we observed large structural genomic variations amongst the isolates which revealed different plasmid contents, active roles for transposase IS3 and IS5 in the deactivation of genes, and mobile prophage elements. Our study shows limited within-patient B. multivorans evolution and high between-patient strain diversity, indicating that an environmental microdiverse reservoir must be present for this endemic strain, in which active diversification is taking place. Furthermore, our analysis also reveals a set of 30 parallel adaptations across multiple patients, indicating that the specific genomic background of a given strain may dictate the route of adaptation within the cystic fibrosis lung.
Keywords
Microbiology, Epidemiology, Cystic fibrosis

Downloads

  • journal.ppat.1009418.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 3.82 MB

Citation

Please use this url to cite or link to this publication:

MLA
Lood, Cédric, et al. “Genomics of an Endemic Cystic Fibrosis Burkholderia Multivorans Strain Reveals Low Within-Patient Evolution but High between-Patient Diversity.” PLOS PATHOGENS, edited by William Navarre, vol. 17, no. 3, 2021, doi:10.1371/journal.ppat.1009418.
APA
Lood, C., Peeters, C., Lamy-Besnier, Q., Wagemans, J., De Vos, D., Proesmans, M., … Vandamme, P. (2021). Genomics of an endemic cystic fibrosis Burkholderia multivorans strain reveals low within-patient evolution but high between-patient diversity. PLOS PATHOGENS, 17(3). https://doi.org/10.1371/journal.ppat.1009418
Chicago author-date
Lood, Cédric, Charlotte Peeters, Quentin Lamy-Besnier, Jeroen Wagemans, Daniel De Vos, Marijke Proesmans, Jean-Paul Pirnay, et al. 2021. “Genomics of an Endemic Cystic Fibrosis Burkholderia Multivorans Strain Reveals Low Within-Patient Evolution but High between-Patient Diversity.” Edited by William Navarre. PLOS PATHOGENS 17 (3). https://doi.org/10.1371/journal.ppat.1009418.
Chicago author-date (all authors)
Lood, Cédric, Charlotte Peeters, Quentin Lamy-Besnier, Jeroen Wagemans, Daniel De Vos, Marijke Proesmans, Jean-Paul Pirnay, Fedoua Echahidi, Denis Piérard, Matthieu Thimmesch, Anca Boeras, Katrien Lagrou, Evelien De Canck, Elke De Wachter, Vera van Noort, Rob Lavigne, and Peter Vandamme. 2021. “Genomics of an Endemic Cystic Fibrosis Burkholderia Multivorans Strain Reveals Low Within-Patient Evolution but High between-Patient Diversity.” Ed by. William Navarre. PLOS PATHOGENS 17 (3). doi:10.1371/journal.ppat.1009418.
Vancouver
1.
Lood C, Peeters C, Lamy-Besnier Q, Wagemans J, De Vos D, Proesmans M, et al. Genomics of an endemic cystic fibrosis Burkholderia multivorans strain reveals low within-patient evolution but high between-patient diversity. Navarre W, editor. PLOS PATHOGENS. 2021;17(3).
IEEE
[1]
C. Lood et al., “Genomics of an endemic cystic fibrosis Burkholderia multivorans strain reveals low within-patient evolution but high between-patient diversity,” PLOS PATHOGENS, vol. 17, no. 3, 2021.
@article{8702379,
  abstract     = {{In many countries, Burkholderia multivorans is the most prevalent species within the Burkholderia cepacia complex (Bcc) found infecting the lungs of patients with cystic fibrosis (CF). Its positive identification is of immediate concern to the health of the patient as it is notoriously hard to eradicate using antibiotics and can cause necrosis of the lung tissues (cepacia syndrome). Infection control measures reduced the prevalence of B. cenocepacia in CF wards, but patients continue to acquire infections by B. multivorans from environmental sources. In most reported cases, the infecting strains are unique except in rare cases in which cross-infection is observed between patients. We report here an endemic strain of B. multivorans with sequence type ST-742 that has been infecting multiple patients, without evidence for cross-infection. We investigated the epidemiology and genomics of this ST-742 strain and show that it is microdiverse, as isolates between-patients exhibit numerous genomic differences, at scales that have not been observed previously when looking at evolutionary trajectories within-patients. Additionally, we found that the specific genomic background of a given strain may dictate the strategy of adaptation within the CF lung.

Burkholderia multivorans is a member of the Burkholderia cepacia complex (Bcc), notorious for its pathogenicity in persons with cystic fibrosis. Epidemiological surveillance suggests that patients predominantly acquire B. multivorans from environmental sources, with rare cases of patient-to-patient transmission. Here we report on the genomic analysis of thirteen isolates from an endemic B. multivorans strain infecting four cystic fibrosis patients treated in different pediatric cystic fibrosis centers in Belgium, with no evidence of cross-infection. All isolates share an identical sequence type (ST-742) but whole genome analysis shows that they exhibit peculiar patterns of genomic diversity between patients. By combining short and long reads sequencing technologies, we highlight key differences in terms of small nucleotide polymorphisms indicative of low rates of adaptive evolution within patient, and well-defined, hundred Kbps-long segments of high enrichment in mutations between patients. In addition, we observed large structural genomic variations amongst the isolates which revealed different plasmid contents, active roles for transposase IS3 and IS5 in the deactivation of genes, and mobile prophage elements. Our study shows limited within-patient B. multivorans evolution and high between-patient strain diversity, indicating that an environmental microdiverse reservoir must be present for this endemic strain, in which active diversification is taking place. Furthermore, our analysis also reveals a set of 30 parallel adaptations across multiple patients, indicating that the specific genomic background of a given strain may dictate the route of adaptation within the cystic fibrosis lung.}},
  articleno    = {{e1009418}},
  author       = {{Lood, Cédric and Peeters, Charlotte and Lamy-Besnier, Quentin and Wagemans, Jeroen and De Vos, Daniel and Proesmans, Marijke and Pirnay, Jean-Paul and Echahidi, Fedoua and Piérard, Denis and Thimmesch, Matthieu and Boeras, Anca and Lagrou, Katrien and De Canck, Evelien and De Wachter, Elke and van Noort, Vera and Lavigne, Rob and Vandamme, Peter}},
  editor       = {{Navarre, William}},
  issn         = {{1553-7366}},
  journal      = {{PLOS PATHOGENS}},
  keywords     = {{Microbiology,Epidemiology,Cystic fibrosis}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{23}},
  title        = {{Genomics of an endemic cystic fibrosis Burkholderia multivorans strain reveals low within-patient evolution but high between-patient diversity}},
  url          = {{http://dx.doi.org/10.1371/journal.ppat.1009418}},
  volume       = {{17}},
  year         = {{2021}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: