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Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis

Nature Reviews Microbiology volume 19, pages 331–342 (2021)Cite this article

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Abstract

Intense genome sequencing of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) airways has shown inefficient eradication of the infecting bacteria, as well as previously undocumented patient-to-patient transmission of adapted clones. However, genome sequencing has limited potential as a predictor of chronic infection and of the adaptive state during infection, and thus there is increasing interest in linking phenotypic traits to the genome sequences. Phenotypic information ranges from genome-wide transcriptomic analysis of patient samples to determination of more specific traits associated with metabolic changes, stress responses, antibiotic resistance and tolerance, biofilm formation and slow growth. Environmental conditions in the CF lung shape both genetic and phenotypic changes of P. aeruginosa during infection. In this Review, we discuss the adaptive and evolutionary trajectories that lead to early diversification and late convergence, which enable P. aeruginosa to succeed in this niche, and we point out how knowledge of these biological features may be used to guide diagnosis and therapy.

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Fig. 1: Adaptation of Pseudomonas aeruginosa in cystic fibrosis airways.
Fig. 2: Metabolic and physiologic adaptation of Pseudomonas aeruginosa to the cystic fibrosis environment.
Fig. 3: Response and adaptation of Pseudomonas aeruginosa to antibiotics and the host immune system.

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Acknowledgements

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), the Novo Nordisk Foundation Center for Biosustainability (CfB), Technical University of Denmark and The Novo Nordisk Foundation (NNF) (grant number NNF10CC1016517). J.A.B was funded by a postdoctoral fellowship from the Whitaker Foundation. H.K.J. was supported by NNF as a clinical research stipend (NNF12OC1015920), Rigshospitalets Rammebevilling 2015–17 (R88-A3537), Lundbeckfonden (R167-2013-15229), NNF (NNF15OC0017444), RegionH Rammebevilling (R144-A5287), Independent Research Fund Denmark/Medical and Health Sciences (FTP-4183-00051) and ‘Savværksejer Jeppe Juhl og Hustru Ovita Juhls mindelegat’.

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  1. Elio Rossi

    Present address: Department of Biosciences, Università degli Studi di Milano, Milan, Italy

Authors and Affiliations

  1. Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark

    Elio Rossi, Lea M. Sommer & Helle Krogh Johansen

  2. The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark

    Ruggero La Rosa, Jennifer A. Bartell, Janus A. J. Haagensen, Søren Molin & Helle Krogh Johansen

  3. Center for Genomic Medicine, Rigshospitalet, Copenhagen, Denmark

    Rasmus L. Marvig

  4. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Helle Krogh Johansen

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  1. Elio Rossi
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All authors contributed to the text of the article. E.R., S.M. and H.K.J. wrote the final version and performed all of the necessary editing.

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Glossary

Clone type

Isolates of the same species that differ in their genomes by fewer than 10,000 single-nucleotide polymorphisms.

Hypermutator phenotype

A phenotype that shows an up to a 1,000-fold increased mutation rate compared with that of wild-type strains.

Expectorates

Cough or spit-out materials from the lower airways.

Bronchoalveolar lavage

A minimally invasive procedure that involves instillation of sterile saline into a segment of the lung, followed by suction and collection of the instillation for analysis. This procedure is typically facilitated by the introduction of a flexible bronchoscope into a segment of the lung.

Chronic obstructive pulmonary disease

A progressive lung disease that worsens over time, characterized by long-term breathing problems and poor airflow. The most common cause of chronic obstructive pulmonary disease is tobacco smoking, with a smaller number of cases due to factors such as air pollution and genetics.

Exacerbations

Worsening of chronic airway disease symptoms caused by a lung infection leading to increased production of secretion.

High-persister

A phenotype describing a substantial increase in the size of the surviving subpopulation during intensive antibiotic treatment without being resistant.

Tandem amplification

A process that occurs in DNA when a sequence of nucleotides is repeated and the repetitions are directly adjacent to each other. Changes in gene copy number are among the most frequent mutational events in all genomes.

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Rossi, E., La Rosa, R., Bartell, J.A. et al. Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis. Nat Rev Microbiol 19, 331–342 (2021). https://doi.org/10.1038/s41579-020-00477-5

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