Host-specific plasmid evolution explains the variable spread of clinical antibiotic-resistance plasmids

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Antibiotic resistance encoded on plasmids poses a significant global health challenge.
• Predicting the long-term spread of plasmids is complex due to factors like plasmid growth costs and horizontal transfer rates.
• Existing models often struggle to account for the dynamic evolution of these traits.

Purpose of the Study:

• To investigate how plasmid stability and spread evolve over time in specific bacterium-plasmid combinations.
• To determine if initial plasmid traits or subsequent evolutionary changes are better predictors of long-term stability.
• To identify the genetic mechanisms underlying strain-specific plasmid evolution.

Main Methods:

• Experimental evolution of *Escherichia coli* with clinical antibiotic-resistance plasmids.
• Mathematical modeling to track long-term plasmid stability beyond antibiotic selection.
• Genome sequencing and genetic manipulation to analyze evolutionary trajectories and identify key genetic changes.

Main Results:

• Plasmid stability traits evolve rapidly in a strain-specific manner, significantly altering spread potential.
• Initial variations in plasmid growth costs and transfer rates were poor predictors of long-term outcomes.
• Strain-dependent (epistatic) effects of genetic changes, including those in mobile elements and pathogenicity islands, were identified as crucial for horizontal transfer.
• Evolutionary trajectories varied significantly across different bacterium-plasmid combinations.

Conclusions:

• Rapid, strain-specific evolution of plasmids can override ancestral phenotypes in predicting long-term stability and spread.
• Understanding these evolutionary dynamics is critical for managing antibiotic resistance.
• Incorporating strain-specific plasmid evolution into models can improve predictions of bacterium-plasmid combination success.