Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to the Dermis.
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.


METHODS
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.


METHODS
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.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Rodrigo J
RJ
Gonzalez
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
Eric H
EH
Weening
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA.
M Chelsea
MC
Lane
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA vlmiller@med.unc.edu.
Virginia L
VL
Miller
D000220:Adaptation, Biological; D000818:Animals; D020405:Dermis / Q000382:microbiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D008810:Mice, Inbred C57BL; D010930:Plague / Q000382:microbiology*; D016019:Survival Analysis; D015010:Yersinia pestis / Q000502:physiology*