The subcutaneous inoculation of pH 6 antigen mutants of Yersinia pestis does not affect virulence and immune response in mice

Anisimov, Andrey P.; Бахтеева, И. В.; Panfertsev, E. A.; Светоч, Т. Э.; Kravchenko, T. B.; Platonov, M. E.; Титарева, Г. М.; Комбарова, Т. И.; Ivanov, Sergey A.; Rakin, Alexander; Amoako, Kingsley K.; Dentovskaya, Svetlana V.

doi:10.1099/jmm.0.005678-0

Cited by 25 publications

(24 citation statements)

References 59 publications

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“…pestis Psa fimbriae were previously found by us and others to bind to respiratory tract epithelial cells and interact with macrophages (31,37). Although the results of previous studies indirectly suggested that the Psa fimbriae are expressed in vivo (7,13,14,35,36), definitive evidence was lacking. In this study we have conclusively demonstrated by immunohistochemistry that the Psa antigen is produced in tissues of Y. pestis-infected mice.…”

Section: Discussioncontrasting

confidence: 44%

Biosafety Level 2 Model of Pneumonic Plague and Protection Studies with F1 and Psa

et al. 2010

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Attenuated Yersinia pestis pgm strains, such as KIM5, lack the siderophore yersiniabactin. Strain KIM5 does not induce significant pneumonia when delivered intranasally. In this study, mice were found to develop pneumonia after intranasal challenge with strain KIM5 when they were injected intraperitoneally with iron dextran, though not with iron sulfate. KIM5-infected mice treated daily with 4 mg iron dextran died in 3 days with severe pneumonia. Pneumonia was less severe if 4 mg iron dextran was administered only once before infection. The best-studied experimental vaccine against plague currently consists of the Yersinia pestis capsular antigen F1 and the type 3 secreted protein LcrV. The F1 antigen was shown to be protective against KIM5 infections in mice administered iron dextran doses leading to light or severe pneumonia, supporting the use of an iron dextran-treated model of pneumonic plague. Since F1 has been reported to be incompletely protective in some primates, and bacterial isolates lacking F1 are still virulent, there has been considerable interest in identifying additional protective subunit immunogens. Here we showed that the highly conserved Psa fimbriae of Y. pestis (also called pH 6 antigen) are expressed in murine organs after infection through the respiratory tract. Studies with iron dextran-treated mice showed that vaccination with the Psa fimbrial protein together with an adjuvant afforded incomplete but significant protection in the mouse model described. Therefore, further investigations to fully characterize the protective properties of the Psa fimbriae are warranted.

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Section: Discussioncontrasting

confidence: 44%

Biosafety Level 2 Model of Pneumonic Plague and Protection Studies with F1 and Psa

et al. 2010

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“…Furthermore, such a pPCP 2 /Dlpp mutant strain exhibited drastically reduced tissue injury and a muted cytokine and chemokine induction in tissue homogenates and sera when compared with equivalent findings in WT, Dlpp and pPCP 2 mutant strains. We opted to cure the pPCP1 plasmid from WT and Dlpp Y. pestis strains rather than selectively delete the pla gene, as pesticin and pesticin-immunity protein do not contribute to the virulence of Y. pestis in the animal model (Anisimov et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2009

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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 Dlpp 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 "

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“…The presence of the Y. pestis virulence plasmids was confirmed via PCR (Table 2). The Δ tatA mutant strain was next passaged through Swiss Webster mice by subcutaneous challenge, as routinely practiced by many labs [31], [33], [34], in order to ensure the genetic stability of the mutant strain after numerous in vitro growth steps needed to construct the mutant strain. The Y. pestis genome is unstable due to the presence of numerous IS 100 elements [35]–[37], and the passage of the mutant through an animal decreases the likelihood of a mixed population [2].…”

Section: Methodsmentioning

confidence: 99%

A Yersinia pestis tat Mutant Is Attenuated in Bubonic and Small-Aerosol Pneumonic Challenge Models of Infection but Not As Attenuated by Intranasal Challenge

et al. 2014

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Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

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The subcutaneous inoculation of pH 6 antigen mutants of Yersinia pestis does not affect virulence and immune response in mice

Cited by 25 publications

References 59 publications

Biosafety Level 2 Model of Pneumonic Plague and Protection Studies with F1 and Psa

Biosafety Level 2 Model of Pneumonic Plague and Protection Studies with F1 and Psa

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

A Yersinia pestis tat Mutant Is Attenuated in Bubonic and Small-Aerosol Pneumonic Challenge Models of Infection but Not As Attenuated by Intranasal Challenge

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