Insights Into The Early Diversification of blaNDM-1 Genetic Contexts Following its Emergence in Acinetobacter species and Spread to Enterobacterales

Abstract

Since its emergence, the New Delhi metallo-{beta}-lactamase (NDM) has become a major global antimicrobial resistance threat, enabling bacterial hosts to resist most {beta}-lactam antibiotics, including carbapenems, and spreading widely across bacterial species and geographic regions. Believed to have originated in Acinetobacter spp., blaNDM subsequently spread to Enterobacterales through mobile genetic elements, despite barriers to lateral gene transfer between these phylogenetically distant taxa. To investigate the genetic diversity and mechanisms underlying this interspecies transfer and subsequent global expansion, we sequenced and characterized 13 blaNDM-1-positive Gram-negative bacterial isolates collected in India in 2007, among the earliest known isolates harboring blaNDM-1. Clonal diversity was observed among both Escherichia coli and Klebsiella pneumoniae isolates. Comprehensive genomic analysis revealed that blaNDM-1 was consistently embedded within a conserved multidrug resistance region, often associated with mobile genetic elements involved in lateral gene transfer. Notably, the insertion sequence ISAba14 was identified in 6 of the 13 sequences, suggesting a potential role in the early dissemination of blaNDM-1 among diverse bacterial hosts. These findings contribute to our understanding of the evolutionary origins and early genetic context of blaNDM-1, highlighting the importance of continued genomic surveillance and functional studies to better understand the persistence and dissemination of carbapenem resistance.