Next-Generation Sequencing-Based Identification of Enterobacter hormaechei as Causative Agent of High Mortality Disease in NOD.Cg- Prkdc scid Il2rg tm1Wjl /SzJ (NSG) Mice.

This article focuses on a high-mortality disease outbreak in NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (NSG) mice, a severely immunodeficient strain widely used in preclinical research. The outbreak was linked to an opportunistic infection by Enterobacter hormaechei, a member of the Enterobacter cloacae complex (ECC), identified through a combination of traditional culture methods and a novel targeted amplicon-based next-generation sequencing (NGS) assay. Clinically affected NSG mice exhibited necrotizing enterocolitis and systemic inflammatory lesions, with significantly higher ECC and E. hormaechei loads compared to unaffected mice. This study highlights the importance of advanced molecular diagnostics for detecting emerging pathogens in immunodeficient mouse models to improve biosecurity, prevent research confounders, and guide treatment strategies.