The role of relA and spoT in Yersinia pestis KIM5+ pathogenicity

Wei Sun, Kenneth L. Roland, Christine G. Branger, Xiaoying Kuang, Roy Curtiss

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The ppGpp molecule is part of a highly conserved regulatory system for mediating the growth response to various environmental conditions. This mechanism may represent a common strategy whereby pathogens such as Yersinia pestis, the causative agent of plague, regulate the virulence gene programs required for invasion, survival and persistence within host cells to match the capacity for growth. The products of the relA and spoT genes carry out ppGpp synthesis. To investigate the role of ppGpp on growth, protein synthesis, gene expression and virulence, we constructed a ΔrelA ΔspoT Y. pestis mutant. The mutant was no longer able to synthesize ppGpp in response to amino acid or carbon starvation, as expected. We also found that it exhibited several novel phenotypes, including a reduced growth rate and autoaggregation at 26°C. In addition, there was a reduction in the level of secretion of key virulence proteins and the mutant was>1,000-fold less virulent than its wild-type parent strain. Mice vaccinated subcutaneously (s.c.) with 2.5×104 CFU of the ΔrelA ΔspoT mutant developed high anti-Y. pestis serum IgG titers, were completely protected against s.c. challenge with 1.5×105 CFU of virulent Y. pestis and partially protected (60% survival) against pulmonary challenge with 2.0×104 CFU of virulent Y. pestis. Our results indicate that ppGpp represents an important virulence determinant in Y. pestis and the ΔrelA ΔspoT mutant strain is a promising vaccine candidate to provide protection against plague.

Original languageEnglish (US)
Article numbere6720
JournalPLoS One
Volume4
Issue number8
DOIs
StatePublished - Aug 24 2009

Fingerprint

Yersinia pestis
Virulence
pathogenicity
virulence
mutants
Genes
Plague
plague
Pathogens
Mutant Proteins
Growth
Gene expression
Carbon
Vaccines
Immunoglobulin G
Amino Acids
Molecules
Starvation
starvation
Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sun, W., Roland, K. L., Branger, C. G., Kuang, X., & Curtiss, R. (2009). The role of relA and spoT in Yersinia pestis KIM5+ pathogenicity. PLoS One, 4(8), [e6720]. https://doi.org/10.1371/journal.pone.0006720

The role of relA and spoT in Yersinia pestis KIM5+ pathogenicity. / Sun, Wei; Roland, Kenneth L.; Branger, Christine G.; Kuang, Xiaoying; Curtiss, Roy.

In: PLoS One, Vol. 4, No. 8, e6720, 24.08.2009.

Research output: Contribution to journalArticle

Sun, W, Roland, KL, Branger, CG, Kuang, X & Curtiss, R 2009, 'The role of relA and spoT in Yersinia pestis KIM5+ pathogenicity', PLoS One, vol. 4, no. 8, e6720. https://doi.org/10.1371/journal.pone.0006720
Sun W, Roland KL, Branger CG, Kuang X, Curtiss R. The role of relA and spoT in Yersinia pestis KIM5+ pathogenicity. PLoS One. 2009 Aug 24;4(8). e6720. https://doi.org/10.1371/journal.pone.0006720
Sun, Wei ; Roland, Kenneth L. ; Branger, Christine G. ; Kuang, Xiaoying ; Curtiss, Roy. / The role of relA and spoT in Yersinia pestis KIM5+ pathogenicity. In: PLoS One. 2009 ; Vol. 4, No. 8.
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