A spontaneous mutation in kdsD, a biosynthesis gene for 3 Deoxy-D-manno-Octulosonic Acid, occurred in a ciprofloxacin resistant strain of Francisella tularensis and caused a high level of attenuation in murine models of tularemia
Fig 10
Pathology of mice challenged by small particle aerosol with F. tularensis.
The strains used for aerosol challenge (Schu S4 WT, CipR, and kdsD::ltrBL1) and the HE stained organ (lung, spleen, and liver) are as indicated. The mice challenged with Schu S4 were collected at Day 5 when all mice had succumbed to infection. The mice challenged with the CipR or kdsD::ltrBL1 mutant survived till the end of the study (Day 21) and displayed no clinical signs of infection. Schu S4 WT: Lung (4x)–multifocal areas of inflammation and necrosis (*); arrow indicates the inset area. Inset (40x)–necrosis admixed with inflammatory cells. Spleen (4x)–diffuse coalescing areas of necrosis (*) affecting red pulp and white pulp. Inset (40x)–necrosis (*) admixed with inflammatory cells; arrow indicates the inset area. Liver (10x)–Single focus of necrosis (*); arrow indicates the inset area. Insert (40x)–necrosis with few inflammatory cells. CipR: Lung (4x)–Diffuse coalescing areas of necrosis (*) with inflammatory cells that extend to the surface of the lung. Spleen (4x)–normal. Liver (10x)–normal. kdsD::ltrBL1: Lung (4x)–foci of necrosis (*) centered on a large airway. Spleen (4x)–normal. Liver (10x)–normal.