Dynamical memory underlies prolonged plasmid persistence after transient antibiotic treatment

Area of Science:

• Microbiology and Evolutionary Biology
• Antimicrobial Resistance (AMR) Dynamics

Background:

• Plasmids are key drivers of antimicrobial resistance (AMR) spread and maintenance.
• Burdensome plasmids often persist despite antibiotic treatment, challenging existing explanations like horizontal transfer or low cost.
• The slow decay of highly burdensome, poorly mobile plasmids remains poorly understood.

Purpose of the Study:

• To investigate the mechanisms behind the prolonged persistence of burdensome plasmids.
• To explore the role of timescale decoupling between plasmid loss and bacterial growth competition.
• To demonstrate how transient antibiotic exposure can manipulate plasmid persistence dynamics.

Main Methods:

• Theoretical modeling using nonlinear dynamical systems to describe the 'ghost effect'.
• Computational simulations to analyze plasmid dynamics under varying conditions.
• Quantitative experiments using both clonal bacterial populations and multi-species communities.

Main Results:

• Demonstrated that the decoupling of slow segregation loss and fast growth competition slows plasmid decay at high initial abundances.
• Identified a 'ghost' state where transient antibiotic pulses eliminate sensitive cells, extending plasmid persistence significantly.
• Observed plasmid persistence extending from days to months under specific experimental conditions.

Conclusions:

• The 'ghost effect' provides a generalizable mechanism explaining prolonged plasmid persistence and ecological memory of antibiotic exposure.
• Transient antibiotic treatments can be strategically used to manipulate plasmid dynamics.
• Highlights the need for proactive strategies to combat AMR spread, considering these persistence mechanisms.