Compensatory mutations improve general permissiveness to antibiotic resistance plasmids

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Horizontal gene transfer via plasmids is a major driver of antibiotic resistance.
• Bacteria often struggle to maintain plasmids, limiting resistance spread.
• Evolutionary mechanisms for improved plasmid persistence are not well understood.

Purpose of the Study:

• Identify evolutionary mechanisms improving plasmid persistence in bacteria.
• Determine if adaptation to one plasmid affects tolerance to others.
• Investigate the genetic basis of enhanced plasmid retention.

Main Methods:

• Experimental evolution of Pseudomonas sp. H2 with multidrug resistance plasmid RP4.
• Joint experimental-modelling approach to assess plasmid persistence and fitness cost.
• Whole-genome sequencing of evolved clones and reconstruction of key mutations.

Main Results:

• Plasmid persistence significantly improved within 600 generations.
• Initial fitness cost of plasmid carriage reversed into a fitness benefit.
• Evolved bacteria showed increased permissiveness to naive plasmids.
• Key mutations identified in accessory helicases and the RNA polymerase β-subunit.

Conclusions:

• Bacterial adaptation can rapidly overcome plasmid-associated fitness costs.
• Evolved plasmid permissiveness facilitates the spread of antibiotic resistance.
• Helicase-plasmid interactions are critical determinants of plasmid persistence and can be modulated by host evolution.