BMHC-1: a novel chromosomally encoded metallo-β-lactamase with potent carbapenemase activity and potential for global dissemination in zoonotic and human pathogens.

OBJECTIVES

Chromosomally encoded metallo-β-lactamases (MBLs) are frequently overlooked in surveillance due to assumed limited transmissibility. We characterized BMHC-1, a novel subclass B1 MBL identified in Riemerella anatipestifer, to evaluate its biochemical properties, structural features and mobilization potential across human, animal and environmental settings.

METHODS

The blaBMHC-1 gene was heterologously expressed in Escherichia coli and R. anatipestifer. Antimicrobial susceptibility, enzyme kinetics and inhibition profiles were determined. The AlphaFold3-predicted structure was used for docking and dynamics simulations to elucidate substrate and inhibitor interactions. Genetic context was analysed via comparative genomics, and mobilization potential was assessed through natural transformation assays.

RESULTS

BMHC-1 conferred high-level resistance to penicillins, extended-spectrum cephalosporins and carbapenems. Imipenem and meropenem MICs reached 256 mg/L, comparable to epidemic NDM-1 and NDM-5 variants. Kinetic assays showed efficient hydrolysis of all tested carbapenems (imipenem kcat/Km = 6.0 × 105 s-1·M-1). Notably, BMHC-1 exhibited markedly reduced sensitivity to EDTA (IC50 = 1.46 mM) compared with NDM-1 (9.52 μM). Structural modelling and MD simulations attributed this to a narrow, deeply buried active site that restricts bulky chelators while accommodating planar carbapenems. Although chromosomal in R. anatipestifer, blaBMHC-1 was widely disseminated globally, predominantly (84.31%) in clinical Elizabethkingia anophelis isolates, where it resides within a conserved integrative and conjugative element (ICE). Natural transformation confirmed the gene's ability to mobilize within R. anatipestifer.

CONCLUSIONS

BMHC-1 is a potent subclass B1 MBL with structural features that confer reduced inhibitor sensitivity. Despite its chromosomal origin in avian pathogens, its embedding within mobilizable ICEs in clinical E. anophelis and capacity for natural transformation pose a significant One Health risk, necessitating its inclusion in global surveillance strategies.