Long-Term Microevolution of Pseudomonas aeruginosa Differs between Mildly and Severely Affected Cystic Fibrosis Lungs

American Journal of Respiratory Cell and Molecular Biology
Jens KlockgetherBurkhard Tümmler

Abstract

Chronic airway infections with Pseudomonas aeruginosa determine morbidity in most individuals with cystic fibrosis (CF). P. aeruginosa may persist for decades in CF lungs, which provides a rare opportunity to study the long-term within-host evolution of a bacterial airway pathogen. In this work, we sought to resolve the genetic adaptation of P. aeruginosa in CF lungs from the onset of colonization until the patient's death or permanent replacement by another P. aeruginosa clone. We followed the microevolution of the first persisting P. aeruginosa clone by whole-genome sequencing of serial isolates from highly divergent clinical courses of airway infection, i.e., a fatal outcome because of respiratory insufficiency within less than 15 years, or a rather normal daily life 25-35 years after acquisition of P. aeruginosa. Nonneutral mutations predominantly emerged in P. aeruginosa genes relevant for protection against and communication with signals from the lung environment, i.e., antibiotic resistance, cell wall components, and two-component systems. Drastic and loss-of-function mutations preferentially happened during the severe courses of infection, and the bacterial lineages of the mild courses more proficiently incorporated ext...Continue Reading

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Citations

Mar 28, 2019·American Journal of Respiratory and Critical Care Medicine·Bonnie W RamseyChristopher H Goss
May 1, 2018·American Journal of Respiratory Cell and Molecular Biology·Craig Winstanley, Michael A Brockhurst
Sep 30, 2020·FEMS Microbiology Reviews·Changhan LeeUte Römling
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Oct 24, 2020·The European Respiratory Journal·Jennifer A BartellHelle Krogh Johansen
Dec 10, 2020·American Journal of Respiratory and Critical Care Medicine·Dustin R LongStephen J Salipante

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