# The rise and global spread of IMP carbapenemases (1996-2023): a genomic epidemiology study

## TL;DR

This study tracks the global spread of IMP carbapenemase genes in bacteria from 1996 to 2023, revealing how these antibiotic resistance genes became widespread.

## Contribution

The study provides a detailed genomic epidemiology of blaIMP genes, identifying key variants and their global or regional spread patterns.

## Key findings

- IMP carbapenemase variants like blaIMP-1 and blaIMP-4 became globally endemic.
- Horizontal gene transfer via mobile elements like integrons and plasmids drove blaIMP dissemination.
- blaIMP-26 and blaIMP-27 are regionally endemic in Southeast Asia and North America.

## Abstract

Infections caused by carbapenemase-producing organisms are a global health threat. IMP carbapenemases are one of the key drivers of these infections but little is known regarding their global epidemiology. We analyse three decades of blaIMP gene spread using sequence data from 4556 genomes collected between 1996–2023. A total of 52 blaIMP variants were identified across 93 bacterial species. We reconstruct the historical emergence and variant-specific epidemiologies of blaIMP genes and showed how key variants (blaIMP-1, blaIMP-4, blaIMP-7, blaIMP-8 and blaIMP-13) achieved global endemicity, while blaIMP-26 and blaIMP-27 became regionally endemic in Southeast Asia and North America, respectively. Dissemination was driven predominantly by horizontal gene transfer facilitated by mobile genetic elements such as class 1 integrons and insertion sequences. These elements mobilised blaIMP genes into 52 distinct plasmid clusters (predominantly IncHI2A, IncN, IncL/M, and IncC), enabling broad inter-species transmission. Despite limited overall cross-source transmission, spillover primarily occurred between human and environmental reservoirs. Structural analysis revealed conserved IMP carbapenemase structure (mean lDDT 0.977) with convergent missense mutations at seven catalytically relevant sites. Our analysis provides a framework for understanding blaIMP dissemination, highlighting their emergence as an important, yet under-recognised, public health threat.

Carbapenemase blaIMP genes between 1996-2023 were analysed across 4,556 genomes, revealing variant-specific epidemiologies and endemicities. Horizontal gene transfer enabled broad inter-species transmission, along with expansion of successful clones.