<p>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 <i>bla</i><sub>IMP</sub> gene spread using sequence data from 4556 genomes collected between 1996–2023. A total of 52 <i>bla</i><sub>IMP</sub> variants were identified across 93 bacterial species. We reconstruct the historical emergence and variant-specific epidemiologies of <i>bla</i><sub>IMP</sub> genes and showed how key variants (<i>bla</i><sub>IMP-1</sub>, <i>bla</i><sub>IMP-4</sub>, <i>bla</i><sub>IMP-7</sub>, <i>bla</i><sub>IMP-8</sub> and <i>bla</i><sub>IMP-13</sub>) achieved global endemicity, while <i>bla</i><sub>IMP-26</sub> and <i>bla</i><sub>IMP-27</sub> 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 <i>bla</i><sub>IMP</sub> 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 <i>bla</i><sub>IMP</sub> dissemination, highlighting their emergence as an important, yet under-recognised, public health threat.</p>

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

  • Ben Vezina,
  • Bhargava Reddy Morampalli,
  • Hoai-An Nguyen,
  • Angela Gomez-Simmonds,
  • Anton Y. Peleg,
  • Nenad Macesic

摘要

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.