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Updated: Apr 24, 2026
Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes
Published on: February 14, 2025
Staphylococcus aureus alters growth activity, autolysis, and antibiotic tolerance in a human host-adapted Pseudomonas
Charlotte Frydenlund Michelsen1, Anne-Mette Juel Christensen1, Martin Saxtorph Bojer2
1Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Abstract:
Interactions among members of polymicrobial infections or between pathogens and the commensal flora may determine disease outcomes. Pseudomonas aeruginosa and Staphylococcus aureus are important opportunistic human pathogens and are both part of the polymicrobial infection communities in human hosts. In this study, we analyzed the in vitro interaction between S. aureus and a collection of P. aeruginosa isolates representing different evolutionary steps of a dominant lineage, DK2, that have evolved through decades of growth in chronically infected patients. While the early adapted P. aeruginosa DK2 strains outcompeted S. aureus during coculture on agar plates, we found that later P. aeruginosa DK2 strains showed a commensal-like interaction, where S. aureus was not inhibited by P. aeruginosa and the growth activity of P. aeruginosa was enhanced in the presence of S. aureus. This effect is mediated by one or more extracellular S. aureus proteins greater than 10 kDa, which also suppressed P. aeruginosa autolysis and prevented killing by clinically relevant antibiotics through promoting small-colony variant (SCV) formation. The commensal interaction was abolished with S. aureus strains mutated in the agr quorum sensing system or in the SarA transcriptional virulence regulator, as well as with strains lacking the proteolytic subunit, ClpP, of the Clp protease. Our results show that during evolution of a dominant cystic fibrosis lineage of P. aeruginosa, a commensal interaction potential with S. aureus has developed.
Insights
Later strains of Pseudomonas aeruginosa evolved to interact commensally with Staphylococcus aureus. This interaction, mediated by S. aureus proteins, suppressed P. aeruginosa autolysis and promoted antibiotic resistance by encouraging small-colony variant formation.
Area of Science:
- Microbiology
- Bacterial Interactions
- Evolutionary Biology
Background:
- Polymicrobial infections involve complex interactions between pathogens and commensal flora, influencing disease outcomes.
- Pseudomonas aeruginosa and Staphylococcus aureus are key opportunistic pathogens frequently found together in human infections.
- Understanding pathogen interactions is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the in vitro interaction between Staphylococcus aureus and evolving strains of Pseudomonas aeruginosa from a cystic fibrosis lineage.
- To determine how P. aeruginosa's interaction with S. aureus changes during its evolutionary adaptation.
- To identify the mechanisms underlying the observed commensal-like interaction.
Main Methods:
- Coculture of S. aureus with various P. aeruginosa DK2 lineage strains on agar plates.
- Analysis of P. aeruginosa growth and S. aureus inhibition.
- Identification of S. aureus-derived factors mediating the interaction using protein size exclusion and genetic mutations.
- Assessment of P. aeruginosa autolysis, small-colony variant (SCV) formation, and antibiotic susceptibility.
Main Results:
- Early P. aeruginosa DK2 strains outcompeted S. aureus, while later strains exhibited a commensal-like interaction.
- Later P. aeruginosa strains showed enhanced growth in the presence of S. aureus, with no inhibition of S. aureus.
- Extracellular S. aureus proteins (>10 kDa) suppressed P. aeruginosa autolysis and promoted SCV formation, conferring antibiotic resistance.
- The commensal interaction was dependent on S. aureus's agr quorum sensing system, SarA regulator, and ClpP protease.
Conclusions:
- Evolution of a dominant P. aeruginosa cystic fibrosis lineage has led to the development of a commensal interaction potential with S. aureus.
- S. aureus-derived factors play a significant role in modulating P. aeruginosa behavior and promoting survival in polymicrobial settings.
- This adaptive interaction has implications for chronic infections and antibiotic resistance, highlighting the dynamic nature of microbial communities.
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