Genomic Changes within a Subset of IncI2 Plasmids Associated with Dissemination of mcr-1 Genes and Other Important...

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• IncI2 plasmids are increasingly associated with antimicrobial resistance genes, including those for last resort antibiotics.
• Their widespread distribution and carriage of critical resistance genes necessitate further investigation into their evolutionary dynamics.

Purpose of the Study:

• To identify specific lineages within the IncI2 plasmid family that exhibit a higher propensity for acquiring antimicrobial resistance genes.
• To investigate the association of mobile genetic elements, such as insertion sequences, with antimicrobial resistance in IncI2 plasmids.

Main Methods:

• Phylogenetic analysis of IncI2 plasmids, including globally distributed and US-sequenced isolates, both resistant and non-resistant to antibiotics.
• Comparative genomics to identify correlations between plasmid lineages, resistance genes, insertion sequences, and potential genomic changes.

Main Results:

• Globally distributed mcr-1-carrying IncI2 plasmids clustered separately from non-resistant IncI2 plasmids and with other IncI2 plasmids carrying extended-spectrum beta-lactamase genes.
• Insertion sequence elements also clustered with resistance-associated IncI2 plasmids, irrespective of direct association with acquired resistance genes.
• Analysis of US surveillance data confirmed distinct clustering of resistant and non-resistant IncI2 plasmids and identified potential genomic changes in core genes correlating with increased foreign DNA acquisition.

Conclusions:

• Specific IncI2 plasmid lineages show a predisposition for acquiring antimicrobial resistance genes, potentially driven by mobile genetic elements.
• Genomic modifications within these prevalent plasmid families may facilitate the increased uptake of foreign DNA, contributing to the spread of antibiotic resistance.