Finally, we developed a computational model simulating the invasion of a bacterial community by a conjugative plasmid harbouring IS elements.

This allowed us to explore a range of parameters of plasmid dissemination, demonstrating that plasmid invasion can promote the IS-driven evolution of AMR

Plasmids are the main disseminators of AMR in natural bacterial communities.

Hence, we wondered whether by disseminating, pOXA-48 may also promote the acquisition of further AMR mechanisms.

This was confirmed by simmulating the invasion of a multi-species Enterobacterales community by pOXA-48.

Next, we aimed to generalize our results beyond our experimental model of pOXA-48 and IS1 by screening >50.000 genomes from databases.

We linked the presence of plasmid-encoded IS elements with the disruption of chromosomal genes leading to AMR for multiple antibiotics and across diverse taxa.

The inactivation of genes is an extended mechanism of AMR. Therefore, we tested the resistance of various clinical isolates of K. pneumoniae against multiple clinically relevant antibiotics.

As expected, the IS encoded in pOXA-48 also increase AMR to kanamycin, ciprofloxacin and chloramphenicol!

Plasmids are enriched in Insertion Sequences (IS). We hypothesized that plasmids promote AMR not only through gene dissemination but also through increased IS-mediated gene inactivation.

We show that a carbapenem-resistance plasmid (pOXA-48) accelerates colistin resistance through IS transposition.