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Updated: Mar 1, 2026

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes
Published on: February 14, 2025
Co-evolution with Staphylococcus aureus leads to lipopolysaccharide alterations in Pseudomonas aeruginosa
Mikael Tognon1,2, Thilo Köhler1,2, Bartosz G Gdaniec1,2
1Transplant Infectious Diseases Unit, University Hospitals of Geneva, Genève, Switzerland.
Insights
Pseudomonas aeruginosa lipopolysaccharide (LPS) mutations provide a fitness advantage when co-colonizing with Staphylococcus aureus in cystic fibrosis airways. These LPS mutations also increase resistance to beta-lactam antibiotics.
Area of Science:
- Microbiology
- Infectious Diseases
- Genomics
Background:
- Bacterial co-colonization in cystic fibrosis (CF) airways involves complex interactions influencing infection outcomes.
- Staphylococcus aureus dominates early CF infections, with Pseudomonas aeruginosa becoming predominant later.
Purpose of the Study:
- To investigate adaptive evolution of P. aeruginosa in response to S. aureus.
- To determine if P. aeruginosa adaptations are specific responses to S. aureus or general environmental responses.
Main Methods:
- Evolving P. aeruginosa populations for 150 generations in the presence and absence of S. aureus.
- Whole-genome sequencing of evolved P. aeruginosa populations and comparison to the ancestor strain.
Main Results:
- Mutations in the Wsp signaling system were found in both conditions, likely due to low oxygen.
- Mutations in lipopolysaccharide (LPS) biosynthesis occurred exclusively in co-cultures with S. aureus, conferring a fitness gain.
- LPS mutations increased resistance to beta-lactam antibiotics and were observed in clinical CF isolates.
Conclusions:
- P. aeruginosa LPS mutations are a direct result of S. aureus-imposed selection in vitro.
- Wsp and LPS mutations found in evolved strains are also present in clinical CF isolates, highlighting their relevance.
- Understanding these interactions is crucial for managing chronic CF lung infections.
Abstract:
Detrimental and beneficial interactions between co-colonizing bacteria may influence the course of infections. In cystic fibrosis (CF) airways, Staphylococcus aureus prevails in childhood, whereas Pseudomonas aeruginosa progressively predominates thereafter. While a range of interactions has been identified, it is unclear if these represent specific adaptations or correlated responses to other aspects of the environment. Here, we investigate how P. aeruginosa adapts to S. aureus by evolving P. aeruginosa in the presence and absence of S. aureus. P. aeruginosa populations that evolved for 150 generations were sequenced and compared to the ancestor strain. Mutations in the Wsp signaling system were identified in both treatments and likely occurred because of low oxygen availability. Despite showing increased killing activity, wsp mutants were less fit in the presence of S. aureus. In contrast, mutations in lipopolysaccharide (LPS) biosynthesis occurred exclusively in co-cultures with S. aureus and conferred a fitness gain in its presence. Moreover, they increased resistance towards beta-lactam antibiotics. Strikingly, both mutations in wsp and LPS genes are observed in clinical isolates from CF-patients. Our results suggest that P. aeruginosa LPS mutations are a direct consequence of S. aureus imposed selection in vitro.
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