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Published on: February 23, 2014
The dependence of the Yersinia pestis capsule on pathogenesis is influenced by the mouse background
Eric H Weening1, Jason S Cathelyn, Greer Kaufman
1Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
Abstract:
Yersinia pestis is a highly pathogenic Gram-negative organism and the causative agent of bubonic and pneumonic plague. Y. pestis is capable of causing major epidemics; thus, there is a need for vaccine targets and a greater understanding of the role of these targets in pathogenesis. Two prime Y. pestis vaccine candidates are the usher-chaperone fimbriae Psa and Caf. Herein we report that Y. pestis requires, in a nonredundant manner, both PsaA and Caf1 to achieve its full pathogenic ability in both pneumonic and bubonic plague in C57BL/6J mice. Deletion of psaA leads to a decrease in the organ bacterial burden and to a significant increase in the 50% lethal dose (LD₅₀) after subcutaneous infection. Deletion of caf1 also leads to a significant decrease in the organ bacterial burden but more importantly leads to a significantly greater increase in the LD₅₀ than was observed for the ΔpsaA mutant strain after subcutaneous infection of C57BL/6J mice. Furthermore, the degree of attenuation of the Δcaf1 mutant strain is mouse background dependent, as the Δcaf1 mutant strain was attenuated to a lesser degree in BALB/cJ mice by the subcutaneous route than in C57BL/6J mice. This observation that the degree of requirement for Caf1 is dependent on the mouse background indicates that the virulence of Y. pestis is dependent on the genetic makeup of its host and provides further support for the hypothesis that PsaA and Caf1 have different targets.
Insights
Yersinia pestis requires both PsaA and Caf1 fimbriae for full virulence in plague models. Deleting these genes significantly reduces bacterial burden and increases lethal dose, highlighting their importance as vaccine targets.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Yersinia pestis causes plague, a devastating epidemic disease.
- Understanding Y. pestis virulence factors is crucial for developing effective vaccines.
- Usher-chaperone fimbriae Psa and Caf are promising vaccine candidates.
Purpose of the Study:
- To investigate the nonredundant roles of PsaA and Caf1 in Y. pestis pathogenesis.
- To evaluate the impact of PsaA and Caf1 on virulence in different plague models.
- To assess the influence of host genetic background on the requirement for these virulence factors.
Main Methods:
- Construction and characterization of Y. pestis mutant strains lacking psaA and caf1.
- Assessment of virulence through organ bacterial burden and lethal dose (LD₅₀) determination in C57BL/6J and BALB/cJ mice.
- Subcutaneous infection models for bubonic and pneumonic plague.
Main Results:
- Deletion of psaA decreased organ bacterial burden and increased LD₅₀ in C57BL/6J mice.
- Deletion of caf1 significantly decreased organ bacterial burden and substantially increased LD₅₀.
- The attenuation of the caf1 deletion mutant was less pronounced in BALB/cJ mice compared to C57BL/6J mice, indicating host-dependent virulence.
Conclusions:
- Both PsaA and Caf1 are essential, nonredundant virulence factors for Y. pestis.
- The differential requirement for Caf1 across mouse backgrounds suggests distinct host-pathogen interactions.
- These findings support PsaA and Caf1 as critical targets for plague vaccine development.
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