A novel α-hemolytic Streptococcus species (Streptococcus azizii sp. nov.) associated with meningoencephalitis in naïve weanling C57BL/6 mice

During 1 year, experimentally naïve C57BL/6NCrl weanlings born to timed-pregnant dams from a single vendor demonstrated markedly increased mortality associated with runting, abnormal gait, and decreased activity. Gram-positive, aerobic, α-hemolytic, coccoid bacteria were isolated from the meninges (n = 16), blood (n = 1), and kidneys (n = 1) of clinically affected weanlings (n = 15); from the uterus (n = 1), meninges (n = 1), and oral cavity (n = 2) of 3 dams; and from the meninges and oral cavity of a clinically affected 86-d-old mouse in the same colony. Multifocal, necrosuppurative meningoencephalitis and ventriculitis with intralesional gram-positive coccoid bacteria were present in all but 2 affected animals. The bacterium also was isolated from the oral cavity of an asymptomatic timed-pregnant dam (1 of 23) from the same vendor and from 8 mice at the vendor's facility. All isolates (n = 25) were identified by using 2 semiautomated rapid-identification systems, one of which consistently identified the causative bacterium as Aerococcus viridans 2 (n = 12) or 3 (n = 13), with probabilities of 55.7% to 98.3%. The bacterium did not grow in 6.5% NaCl at 10 °C, thus suggesting a Streptococcus species. Partial 16S rRNA sequencing of 4 isolates suggested S. hyointestinalis (probability, 93.4%) and S. gallinaceus (99.5%). Full 16S rRNA sequences for 3 isolates identified the bacterium as a novel Streptococcus species most closely related to S. acidominimus strain LGM (96.5%) and Streptococcus species strain Smarlab 3301444 (96.3%) and for which we propose the name S. azizii

Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism

Hereditary forms of iron-deficiency anemia, including animal models, have taught us much about the normal physiologic control of iron metabolism. However, the discovery of new informative mutants is limited by the natural mutation frequency. To address this limitation, we have developed a screen for heritable abnormalities of red blood cell morphology in mice with single-nucleotide changes induced by the chemical mutagen ethylnitrosourea (ENU). We now describe the first strain, fragile-red, with hypochromic microcytic anemia resulting from a Y228H sub-stitution in the ferrireductase Steap3 (Steap3Y288H). Analysis of the Steap3Y288H mutant identifies a conserved motif required for targeting Steap3 to internal compartments and highlights how phenotypic screens linked to mutagenesis can identify new functional variants in erythropoiesis and ascribe function to previously unidentified motifs