NDM-1-producing Enterobacter hormaechei ST145 in Italy: genomic characterization of a multidrug-resistant high-risk clone

Background and objectives Enterobacter hormaechei, a member of the Enterobacter cloacae complex (ECC), is increasingly recognized as an opportunistic pathogen associated with multidrug resistance and nosocomial infections. The emergence of carbapenemase-producing ECC, particularly those harbouring blaNDM-1, represents a significant public health concern. This study aims to provide a comprehensive genomic characterization of an NDM-1-producing E. hormaechei strain (VDL/23) isolated from the bloodstream of a hospitalized patient in Italy. Methods The isolate underwent hybrid WGS using Illumina short reads and Oxford Nanopore long reads. Genomic analyses were performed to characterize the resistome, virulome, plasmid content and associated mobile genetic elements. Conjugation assays were conducted using Escherichia coli K-12 as the recipient strain to assess plasmid transferability. Results WGS identified the isolate as E. hormaechei subsp. hoffmannii ST145, a lineage sporadically reported worldwide but not previously described in Italy. The genome comprised a chromosome and three plasmids (pVDL/23-1, pVDL/23-2, pVDL/23-3). Chromosomal resistance included blaACT-90, fosA and oqxAB, while the IncF-type plasmid pVDL/23-2 carried the main acquired resistance genes, including blaNDM-1, blaCTX-M-15, blaOXA-1 and additional determinants for aminoglycoside, trimethoprim and chloramphenicol resistance. Multiple insertion sequences and IncF replicons supported a mobile genetic context, and conjugation assays confirmed plasmid-mediated transfer of resistance. Conclusions To the best of our knowledge, this study reports the first identification of an NDM-1-producing E. hormaechei ST145 isolate in Italy. The coexistence of extensive resistance determinants and mobile genetic elements highlights the emergence of a high-risk lineage and reinforces the need for genomic surveillance and infection control strategies to limit its dissemination in healthcare settings.