Extensive antimicrobial resistance mobilization via multicopy plasmid encapsidation mediated by temperate phages

Area of Science:

• Bacteriology
• Molecular Biology
• Genetics

Background:

• Antimicrobial resistance (AMR) poses a significant global health threat.
• Mobile genetic elements (MGEs), including plasmids and phages, play a crucial role in the dissemination of AMR genes.
• The role of multicopy plasmids in AMR gene mobilization, particularly their interaction with phages, requires further elucidation.

Purpose of the Study:

• To investigate the significance of multicopy plasmids in the context of antimicrobial resistance.
• To assess the mobilization of antimicrobial resistance genes mediated by phage particles.
• To evaluate the efficiency of AMR gene transfer facilitated by the interplay between multicopy plasmids and phages.

Main Methods:

• Analysis of plasmid databases and annotated genes.
• Transformation of Escherichia coli with plasmids carrying the armA gene (aminoglycoside resistance marker) and lysogenic phages.
• Quantification of armA gene encapsidation into phage particles using qRT-PCR and Southern blotting upon phage induction.

Main Results:

• Multicopy plasmids harbor a substantial number of clinically relevant antimicrobial resistance genes.
• Sixty percent of these multicopy plasmids lack mobility (MOB) genes.
• Mobilization of the armA gene into phage capsids was up to 10,000 times more frequent from multicopy plasmids compared to low-copy-number plasmids.

Conclusions:

• Multicopy plasmids represent a significant reservoir for emerging antimicrobial resistance genes.
• The combination of multicopy plasmids and phages constitutes a novel and highly efficient pathway for the transmission of antimicrobial resistance genes.
• Further research into this plasmid-phage interaction is warranted to understand and combat the spread of antimicrobial resistance.