Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Multidrug resistant bacterial pathogens are a significant global health concern.
• Conjugative plasmids accelerate the spread of antibiotic resistance, particularly to last-resort antibiotics.
• While antibiotic selection drives plasmid-host adaptation, general evolutionary mechanisms remain unclear.

Purpose of the Study:

• To investigate general evolutionary patterns in plasmid-bacteria interactions.
• To identify common mechanisms underlying plasmid persistence and stabilization.
• To explore potential targets for novel therapies against antibiotic resistance.

Main Methods:

• Experimental evolution study of a large conjugative resistance plasmid and its bacterial host.
• Comparison of evolutionary trajectories between conjugative plasmids and non-conjugative replicons.
• Analysis of genetic mutations and mobile genetic element acquisition in evolved plasmid-host systems.

Main Results:

• Conjugative resistance plasmids and their mini-replicons share similar evolutionary paths across different species.
• Three distinct adaptive strategies were identified that increase plasmid persistence: mutations in the replication protein gene (trfA1), acquisition of a toxin-antitoxin system via transposon, and host mutations in the fur gene.
• These identified mechanisms are common to other plasmid-host pairs, suggesting conserved stabilization strategies.

Conclusions:

• Plasmid evolution exhibits common patterns, irrespective of conjugative ability.
• Identified adaptive mechanisms (trfA1 mutations, toxin-antitoxin systems, fur mutations) are key drivers of plasmid stabilization.
• Understanding these common mechanisms could lead to new therapeutic strategies to combat antibiotic resistance spread.