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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.
Abstract:
Dissemination of Yersinia pseudotuberculosis within mice after oral inoculation was analyzed. Y. pseudotuberculosis translocated to organs such as the liver and spleen shortly after oral inoculation, but was quickly cleared. In contrast, a second temporally distinct bacterial translocation event resulted in successful hepatosplenic replication of the bacteria. Replicating pools of bacteria could be established in these organs in mouse mutants that lacked Peyer's patches. These animals frequently had sterile mesenteric lymph nodes, a finding consistent with translocation taking place independently of regional lymph node colonization. In further contradiction to accepted models for dissemination of enteropathogens, clonal analysis revealed that bacteria causing disease in the spleen and liver of C57BL/6J mice were derived from populations located outside the intestinal lymph nodes. Replication of bacteria in the intestine before translocation appeared critical for dissemination, as transient selective suppression by streptomycin of bacterial growth in the intestine delayed dissemination of Y. pseudotuberculosis. These results collectively indicate that hepatosplenic colonization appears intimately connected with the ability of Y. pseudotuberculosis to successfully establish replication in the intestinal lumen and does not result from ordered spread leading from the intestine to regional lymph nodes before dissemination.
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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