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 bla(IMP) gene spread using sequence data from 4556 genomes collected between 1996-2023. A total of 52 bla(IMP) variants were identified across 93 bacterial species. We reconstruct the historical emergence and variant-specific epidemiologies of bla(IMP) genes and showed how key variants (bla(IMP-1), bla(IMP-4), bla(IMP-7), bla(IMP-8) and bla(IMP-13)) achieved global endemicity, while bla(IMP-26) and bla(IMP-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 bla(IMP) 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 bla(IMP) dissemination, highlighting their emergence as an important, yet under-recognised, public health threat.