Yersinia pseudotuberculosis disseminates directly from a replicating bacterial pool in the intestine

Penelope D Barnes1, Molly A Bergman, Joan Mecsas

  • 1Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, MA 02111, USA.

Insights

Yersinia pseudotuberculosis disseminates to the liver and spleen through a novel pathway. Intestinal replication, not lymph node spread, is critical for successful hepatosplenic colonization in mice.

Area of Science:

  • Microbiology
  • Immunology
  • Pathogen Dissemination

Background:

  • Understanding pathogen dissemination is crucial for developing effective treatments.
  • Yersinia pseudotuberculosis is an enteropathogen with complex dissemination routes.
  • Existing models suggest ordered spread from the intestine to lymph nodes.

Purpose of the Study:

  • To elucidate the dissemination pathway of Yersinia pseudotuberculosis after oral inoculation in mice.
  • To investigate the role of intestinal replication and lymph nodes in Y. pseudotuberculosis spread.
  • To challenge established models of enteropathogen dissemination.

Main Methods:

  • Oral inoculation of Yersinia pseudotuberculosis in C57BL/6J mice and mouse mutants lacking Peyer's patches.
  • Analysis of bacterial translocation to organs like the liver and spleen.
  • Clonal analysis to trace bacterial populations.
  • Selective suppression of intestinal bacterial growth using streptomycin.

Main Results:

  • Y. pseudotuberculosis initially translocated to the liver and spleen but was cleared.
  • A second translocation event led to successful hepatosplenic replication, especially in mice lacking Peyer's patches.
  • Intestinal replication prior to translocation was critical for dissemination.
  • Bacterial populations in the spleen and liver originated from outside intestinal lymph nodes.

Conclusions:

  • Hepatosplenic colonization by Y. pseudotuberculosis is linked to intestinal replication, not lymph node colonization.
  • Dissemination occurs independently of regional lymph node spread.
  • The findings contradict traditional models of enteropathogen dissemination.

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