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Updated: Apr 13, 2026
Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to the Dermis
Rodrigo J Gonzalez1, Eric H Weening1, M Chelsea Lane1
1Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Unlabelled:
Vector-borne pathogens are inoculated in the skin of mammals, most likely in the dermis. Despite this, subcutaneous (s.c.) models of infection are broadly used in many fields, including Yersinia pestis pathogenesis. We expand on a previous report where we implemented intradermal (i.d.) inoculations to study bacterial dissemination during bubonic plague and compare this model with an s.c.
Model:
We found that i.d. inoculations result in faster kinetics of infection and that bacterial dose influenced mouse survival after i.d. but not s.c. inoculation. Moreover, a deletion mutant of rovA, previously shown to be moderately attenuated in the s.c. model, was severely attenuated in the i.d.
Model:
Lastly, based on previous observations where a population bottleneck from the skin to lymph nodes was observed after i.d., but not after s.c., inoculations, we used the latter model as a strategy to identify an additional bottleneck in bacterial dissemination from lymph nodes to the bloodstream. Our data indicate that the more biologically relevant i.d. model of bubonic plague differs significantly from the s.c. model in multiple aspects of infection. These findings reveal adaptations of Y. pestis to the dermis and how these adaptations can define the progression of disease. They also emphasize the importance of using a relevant route of infection when addressing host-pathogen interactions.
Insights
The intradermal (i.d.) inoculation model for bubonic plague provides faster infection kinetics and reveals bacterial adaptations to the dermis, differing significantly from subcutaneous (s.c.) models.
Area of Science:
- Microbiology
- Immunology
- Pathogen Dynamics
Background:
- Vector-borne pathogens infect mammalian skin, primarily the dermis.
- Subcutaneous (s.c.) inoculation models are commonly used for studying bacterial pathogenesis, including Yersinia pestis.
- Intradermal (i.d.) inoculation offers a more biologically relevant route for studying skin infections.
Purpose of the Study:
- To compare the i.d. and s.c. inoculation models for Yersinia pestis.
- To investigate bacterial dissemination and host-pathogen interactions using a more relevant infection route.
- To identify bottlenecks in bacterial dissemination during bubonic plague.
Main Methods:
- Comparison of i.d. versus s.c. inoculation of Yersinia pestis in a mammalian model.
- Assessment of infection kinetics, mouse survival, and bacterial dose-response.
- Evaluation of a rovA deletion mutant's virulence in both i.d. and s.c. models.
- Identification of dissemination bottlenecks from skin to lymph nodes and lymph nodes to bloodstream.
Main Results:
- i.d. inoculations resulted in faster infection kinetics compared to s.c.
- Bacterial dose significantly influenced survival after i.d. but not s.c. inoculation.
- A Yersinia pestis rovA deletion mutant showed severe attenuation in the i.d. model, unlike the s.c. model.
- The i.d. model revealed a population bottleneck from skin to lymph nodes, and identified an additional bottleneck from lymph nodes to the bloodstream.
Conclusions:
- The i.d. model is more biologically relevant for studying bubonic plague than the s.c. model.
- Yersinia pestis adaptations to the dermis significantly influence disease progression.
- The choice of inoculation route is critical for accurately studying host-pathogen interactions and bacterial dissemination.
