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

We describe a high mortality disease outbreak caused by an opportunistic bacterial infection in NSG mice. Affected animals exhibited perianal fecal staining, dehydration, and wasting. Histopathologic lesions included a primary necrotizing enterocolitis, with inflammatory and necrotizing lesions also occurring in the liver, kidneys, heart, and brain of some mice. All affected individuals tested negative for known opportunistic pathogens of immunodeficient mice. We initially identified a member of Enterobacter cloacae complex (ECC) in association with the outbreak by traditional diagnostics. ECC was cultured from extraintestinal organs, both with and without histopathologic lesions, suggesting bacteremia. Infrared spectroscopy and MALDI-TOF mass spectrometry demonstrated that isolates from the outbreak shared molecular features and likely a common origin. We subsequently hypothesized that advanced sequencing methods would identify a single species of ECC associated with clinical disease. Using a novel targeted amplicon-based next-generation sequencing assay, we identified Enterobacter hormaechei in association with this outbreak. Knowledge of this organism as a potential opportunistic pathogen in NSG mice is critical for preclinical studies to prevent loss of animals and confounding of research.PMID:38477038 | DOI:10.1177/01926233241231286

Source: Toxicologic Pathology - March 13, 2024 Category: Pathology Authors: Catherine Si Kourtney Nickerson Taylor Simmons Parker Denton M Russell Nichols Robert C Dysko Mark Hoenerhoff Rinosh Mani Cheryl Woods Kenneth S Henderson Zachary T Freeman Source Type: research