Compensatory evolution of Pseudomonas aeruginosa’s slow growth phenotype suggests mechanisms of adaptation in cystic fibrosis

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Abstract

Long-term infection of the airways of cystic fibrosis patients with Pseudomonas aeruginosa is often accompanied by a reduction in bacterial growth rate. This reduction has been hypothesised to increase within-patient fitness and overall persistence of the pathogen. Here, we apply adaptive laboratory evolution to revert the slow growth phenotype of P. aeruginosa clinical strains back to a high growth rate. We identify several evolutionary trajectories and mechanisms leading to fast growth caused by transcriptional and mutational changes, which depend on the stage of adaptation of the strain. Return to high growth rate increases antibiotic susceptibility, which is only partially dependent on reversion of mutations or changes in the transcriptional profile of genes known to be linked to antibiotic resistance. We propose that similar mechanisms and evolutionary trajectories, in reverse direction, may be involved in pathogen adaptation and the establishment of chronic infections in the antibiotic-treated airways of cystic fibrosis patients.

Original languageEnglish
Article number3186
JournalNature Communications
Volume12
Issue number1
Number of pages15
ISSN2041-1723
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
This research was funded by the “Cystic Fibrosis Foundation” (CFF), grant number MOLIN18G0, the “Cystic Fibrosis Trust”, grant number Strategic Research Centre Award—2019—SRC 017, by the “Novo Nordisk Foundation Center for Biosustainability (CfB)”, Technical University of Denmark and by “The Novo Nordisk Foundation”, NNF grant number NNF10CC1016517. H.K.J. was supported by The Novo Nordisk Foundation as a clinical research stipend (NNF12OC1015920), by Rigshospitalets Ramme-bevilling 2015–17 (R88-A3537), by Lundbeckfonden (R167-2013-15229), by Novo Nordisk Foundation (NNF15OC0017444), by RegionH Rammebevilling (R144-A5287), by Independent Research Fund Denmark/Medical and Health Sciences (FTP-4183-00051) and by ‘Savværksejer Jeppe Juhl og Hustru Ovita Juhls mindelegat’.

Publisher Copyright:
© 2021, The Author(s).

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