1887

Abstract

Deletion of the murein (Braun) lipoprotein gene, , attenuates the CO92 strain in mouse models of bubonic and pneumonic plague. In this report, we characterized the virulence of strains from which the plasminogen activating protease ()-encoding pPCP1 plasmid was cured from either the wild-type (WT) or the Δ mutant strain of CO92 in the mouse model of pneumonic infection. We noted a significantly increased survival rate in mice infected with the pPCP mutant strain up to a dose of 5000 LD. Additionally, mice challenged with the pPCP strain had substantially less tissue injury and a strong decrease in the levels of most cytokines and chemokines in tissue homogenates and sera when compared with the WT-infected group. Importantly, the pPCP mutant strain was detectable in high numbers in the livers and spleens of some of the infected mice. In the lungs of pPCP mutant-challenged animals, however, bacterial numbers dropped at 48 h after infection when compared with tissue homogenates from 1 h post-infection. Similarly, we noted that this mutant was unable to survive within murine macrophages in an assay, whereas survivability of the pPCP mutant within the macrophage environment was similar to that of the WT. Taken together, our data indicated that a significant and possibly synergistic attenuation in bacterial virulence occurred in a mouse model of pneumonic plague when both the gene and the virulence plasmid pPCP1 encoding the gene were deleted from .

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2009-10-01
2019-12-08
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