Plasmid-encoded insertion sequences promote rapid adaptation in clinical enterobacteria

Area of Science:

• Microbiology
• Bacterial Genetics
• Evolutionary Biology

Background:

• Plasmids are key drivers of bacterial evolution, primarily through horizontal gene transfer.
• Their role in intragenomic adaptation and evolution beyond gene transfer is less understood.
• The conjugative plasmid pOXA-48 is prevalent in multidrug-resistant clinical bacteria.

Purpose of the Study:

• To investigate how the pOXA-48 plasmid influences the evolution of multidrug-resistant enterobacteria.
• To explore mechanisms of bacterial adaptation mediated by plasmids beyond horizontal gene transfer.

Main Methods:

• Experimental evolution studies.
• Analysis of bacterial evolution within patients.
• Investigating plasmid-encoded insertion sequence 1 (IS1) transposition dynamics.

Main Results:

• The pOXA-48 plasmid facilitates bacterial evolution via transposition of its encoded IS1 elements.
• IS1-mediated gene inactivation accelerates adaptation rates in vitro and in the gut microbiota.
• A negative feedback loop regulating IS1 transposition based on genomic copy number was identified.

Conclusions:

• Plasmid-mediated IS1 transposition is a significant mechanism for rapid bacterial adaptation.
• This highlights an underappreciated role of plasmids in bacterial evolution.
• Findings are relevant given the abundance of IS elements on bacterial plasmids.