Plasmid-encoded insertion sequences promote rapid adaptation in clinical enterobacteria

Area of Science:

• Bacterial genetics and evolution
• Microbial genomics
• Horizontal gene transfer mechanisms

Background:

• Plasmids are key drivers of bacterial evolution, primarily through horizontal gene transfer (HGT).
• Their role in intragenomic adaptation beyond HGT is less understood.
• The pOXA-48 plasmid is a significant factor in multidrug resistance among clinical bacteria.

Purpose of the Study:

• To investigate how the pOXA-48 plasmid influences the evolution of multidrug-resistant clinical enterobacteria.
• To explore mechanisms of bacterial adaptation mediated by plasmids beyond HGT.
• To understand the role of insertion sequences in plasmid-driven evolution.

Main Methods:

• Experimental evolution studies with clinical enterobacteria carrying the pOXA-48 plasmid.
• Within-patient evolution analysis in gut microbiota.
• Investigating the mechanism of IS1 transposition and its regulation.

Main Results:

• Plasmid pOXA-48 facilitates bacterial evolution via transposition of its encoded insertion sequence 1 (IS1) elements.
• IS1-mediated gene inactivation enhances adaptation rates in vitro and within the gut microbiota.
• A negative feedback loop, regulated by IS1 copy number, controls plasmid-mediated IS1 transposition.

Conclusions:

• Plasmid-mediated IS transposition is a significant mechanism for rapid bacterial adaptation.
• This process contributes to the evolution of multidrug-resistant clinical strains.
• Insertion sequence elements on plasmids play a critical role in bacterial evolution.