Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation
Abstract
Colonization of the lungs of cystic fibrosis (CF) patients by the opportunistic bacterial pathogen Pseudomonas aeruginosa is the principal cause of mortality in CF populations. Pseudomonas aeruginosa infections generally persist despite the use of long-term antibiotic therapy. This has been explained by postulating that P. aeruginosa forms an antibiotic-resistant biofilm consisting of bacterial communities embedded in an exopolysaccharide matrix. Alternatively, it has been proposed that resistant P. aeruginosa variants may be selected in the CF respiratory tract by antimicrobial therapy itself. Here we report that both explanations are correct, and are interrelated. We found that antibiotic-resistant phenotypic variants of P. aeruginosa with enhanced ability to form biofilms arise at high frequency both in vitro and in the lungs of CF patients. We also identified a regulatory protein (PvrR) that controls the conversion between antibiotic-resistant and antibiotic-susceptible forms. Compounds that affect PvrR function could have an important role in the treatment of CF infections.
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SCV is highly autoaggregative and resistant to antibiotics, arises at high frequency in vivo, but can revert to antibiotic-sensitive wild-type phenotype.
“This variant is highly autoaggregative and resistant to antibiotics and arises at high frequency in vivo, but can revert back to an antibiotic-sensitive, wild-type phenotype [133].”
From Bacterial autoaggregation (2018) · cites this paper as [133]
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- Authors
- Drenkard, E., & Ausubel, F. M.
- Affiliations
- Harvard University (US)
- Corresponding author
- Ausubel, Frederick M.
- Venue
- Nature
- Published
- 2002-04
- Volume
- 416
- Issue
- 6882
- Pages
- 740-743
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2003343094
- Cited by
- 997
- References
- 28
- Citations by year
- 2026: 10 · 2025: 27 · 2024: 23 · 2023: 17 · 2022: 36 · 2021: 36 · 2020: 39 · 2019: 44 · 2018: 42 · 2017: 55 · 2016: 62 · 2015: 51 · 2014: 57 · 2013: 45 · 2012: 40
- FWCI
- 18.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Pseudomonas aeruginosa, biofilm formation, antibiotic resistance, cystic fibrosis, phenotypic variability, exopolysaccharide matrix, bacterial persistence, antimicrobial therapy, opportunistic lung infection, regulatory proteins
- MeSH terms
- Anti-Bacterial Agents, Bacterial Adhesion, Cloning, Molecular, Cystic Fibrosis, Genes, Bacterial, Humans, Kanamycin Resistance, Lung, Microbial Sensitivity Tests, Models, Biological, Molecular Sequence Data, Mutation, Phenotype, Pseudomonas aeruginosa, Selection, Genetic, Sodium Chloride, Temperature, Genetic Variation, Open Reading Frames, Biofilms, Drug Resistance, Bacterial
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