Unique Presentations of Burkholderia gladioli Infections in Several Strains of Immunocompromised Mice

Abstract

Four strains of experimentally naïve mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ [NSG], NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ[NRG], B6.129S(Cg)-Stat1tm1Dlv/J [STAT1−/−], and B6.129S7-Ifngr1tm1Agt/J [IFNγR−/−] housed in a barrier facility developedunusual and seemingly unrelated clinical signs. Young NSG/NRG mice (n = 49, mean age = 4 ± 0.4 mo) exhibited nonspecificclinical signs of moderate-to-severe lethargy, hunched posture, decreased body condition, and pallor. In contrast to the NSG/NRGmice, the STAT1−/− and IFNγR−/−mice (n = 5) developed large subcutaneous abscesses on the head and neck. These micewere euthanized, and samples were collected for culture. NSG/NRG mice had moderate-markedly enlarged livers (20 of49, 40%) and spleens (17 of 49, 35%). The livers contained multiple, variably-sized, tan regions throughout all lobes. Histologyrevealed necrotizing hepatitis (13 of 17, 77%), splenic and hepatic extramedullary hematopoiesis (17 of 17, 100%), glomerularhistiocytosis (6 of 17, 35%), and metritis (6 of 11, 55%) with perivascular inflammation, suggesting hematogenous spreadDifferentials for these lesions included mouse hepatitis virus, ectromelia virus, Pseudomonas aeruginosa, Salmonella spp.,and Clostridium piliforme. Burkholderia gladioli was cultured from liver lesions and subcutaneous abscesses and confirmedwith 16S ribosomal RNA sequencing. After completing systematic testing of the environment, failure of the water autoclavecycle was suspected as the cause of the outbreak. To address the situation, individually ventilated racks were sanitized andnew breeders were purchased; these actions dramatically reduced B. gladioli infections. The current literature contains fewreports of B. gladioli infections in immunocompromised mice, and its typical presentation is torticollis and rolling. B. gladioliinfection is a potential differential for subcutaneous abscesses, hepatitis, and splenomegaly in immunocompromised mice.Careful monitoring of sterilization techniques is essential to prevent such infections in a barrier facility.