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Updated: May 19, 2026

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes
Published on: February 14, 2025
Phenotype switching is a natural consequence of Staphylococcus aureus replication.
1MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom. a.edwards@imperial.ac.uk
Staphylococcus aureus frequently switches to a small-colony-variant (SCV) phenotype, which is antibiotic-resistant. This phenotype switching is a normal part of the bacterium's life cycle, providing resistance against antibiotics.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Antimicrobial Resistance
Background:
- Staphylococcus aureus exhibits phenotype switching from normal colony phenotype (NCP) to small-colony-variant (SCV) in vivo.
- SCVs are slow-growing, antibiotic-resistant, and associated with persistent infections.
- The trigger for S. aureus phenotype switching (constitutive vs. environmental stimuli) remains unclear.
Purpose of the Study:
- To investigate the mechanism and conditions underlying Staphylococcus aureus phenotype switching.
- To determine if phenotype switching is a constitutive process or triggered by environmental factors.
- To elucidate the role of SCV emergence in bacterial survival and antibiotic resistance.
Main Methods:
- Culturing diverse S. aureus strains without selective pressure.
- Observing SCV emergence during NCP growth phases.
- Treating replicating bacteria with gentamicin to assess SCV replication and stability.
- Analyzing bidirectional phenotype switching and SCV turnover.
Main Results:
- A gentamicin-resistant SCV subpopulation consistently emerged during NCP growth, increasing until stationary phase.
- Gentamicin initially decreased SCV numbers by inhibiting NCP replication, but SCV populations re-established through selection and replication.
- Phenotype switching was bidirectional and occurred frequently during NCP replication in the absence of selective pressure, leading to SCV turnover.
Conclusions:
- Staphylococcus aureus phenotype switching is a constitutive process generating a dynamic, antibiotic-resistant SCV subpopulation.
- SCVs can revert to the parental NCP phenotype, indicating a reversible switching mechanism.
- SCV emergence is a normal aspect of the S. aureus life cycle, conferring a survival advantage against antibiotic exposure.
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