Deletion of Braun lipoprotein gene (lpp) and curing of plasmid pPCP1 dramatically alter the virulence of Yersinia pestis CO92 in a mouse model of pneumonic plague

Stacy L. Agar, Jian Sha, Wallace B. Baze, Tatiana E. Erova, Sheri M. Foltz, Giovanni Suarez, Shaofei Wang, Ashok Chopra

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Abstract

Deletion of the murein (Braun) lipoprotein gene, lpp, attenuates the Yersinia pestis 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 (pla)-encoding pPCP1 plasmid was cured from either the wild-type (WT) or the Δ/pp mutant strain of Y. pestis CO92 in the mouse model of pneumonic infection. We noted a significantly increased survival rate in mice infected with the Y. pestis pPCP-/Δ/pp mutant strain up to a dose of 5000 LD50. Additionally, mice challenged with the pPCP-/ Δ/pp 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 Y. pestis pPCP-/Δ/pp mutant strain was detectable in high numbers in the livers and spleens of some of the infected mice. In the lungs of pPCP-/Δ/pp 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 in vitro 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 lpp gene and the virulence plasmid pPCP1 encoding the pla gene were deleted from Y. pestis.

Original languageEnglish (US)
Pages (from-to)3247-3259
Number of pages13
JournalMicrobiology
Volume155
Issue number10
DOIs
StatePublished - 2009

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Yersinia pestis
Plague
Lipoproteins
Virulence
Plasmids
Genes
Plasminogen
Peptide Hydrolases
Infection
Macrophages
Lung
Peptidoglycan
Lethal Dose 50
Chemokines
Spleen
Cytokines
Liver
Wounds and Injuries
Serum

ASJC Scopus subject areas

  • Microbiology

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Deletion of Braun lipoprotein gene (lpp) and curing of plasmid pPCP1 dramatically alter the virulence of Yersinia pestis CO92 in a mouse model of pneumonic plague. / Agar, Stacy L.; Sha, Jian; Baze, Wallace B.; Erova, Tatiana E.; Foltz, Sheri M.; Suarez, Giovanni; Wang, Shaofei; Chopra, Ashok.

In: Microbiology, Vol. 155, No. 10, 2009, p. 3247-3259.

Research output: Contribution to journalArticle

Agar, Stacy L. ; Sha, Jian ; Baze, Wallace B. ; Erova, Tatiana E. ; Foltz, Sheri M. ; Suarez, Giovanni ; Wang, Shaofei ; Chopra, Ashok. / Deletion of Braun lipoprotein gene (lpp) and curing of plasmid pPCP1 dramatically alter the virulence of Yersinia pestis CO92 in a mouse model of pneumonic plague. In: Microbiology. 2009 ; Vol. 155, No. 10. pp. 3247-3259.
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