Pseudogenization of the Secreted Effector Gene sseI Confers Rapid Systemic Dissemination of S. Typhimurium ST313 within Migratory Dendritic Cells

Publication date: 8 February 2017
Source:Cell Host & Microbe, Volume 21, Issue 2
Author(s): Sarah E. Carden, Gregory T. Walker, Jared Honeycutt, Kyler Lugo, Trung Pham, Amanda Jacobson, Donna Bouley, Juliana Idoyaga, Renee M. Tsolis, Denise Monack
Genome degradation correlates with host adaptation and systemic disease in Salmonella. Most lineages of the S. enterica subspecies Typhimurium cause gastroenteritis in humans; however, the recently emerged ST313 lineage II pathovar commonly causes systemic bacteremia in sub-Saharan Africa. ST313 lineage II displays genome degradation compared to gastroenteritis-associated lineages; yet, the mechanisms and causal genetic differences mediating these infection phenotypes are largely unknown. We find that the ST313 isolate D23580 hyperdisseminates from the gut to systemic sites, such as the mesenteric lymph nodes (MLNs), via CD11b⁺ migratory dendritic cells (DCs). This hyperdissemination was facilitated by the loss of sseI, which encodes an effector that inhibits DC migration in gastroenteritis-associated isolates. Expressing functional SseI in D23580 reduced the number of infected migratory DCs and bacteria in the MLN. Our study reveals a mechanism linking pseudogenization of effectors with the evolution of niche adaptation in a bacterial pathogen.

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Teaser

Genome degradation is associated with host adaptation in bacteria. Carden et al. show that the bacteremia-associated ST313 Salmonella Typhimurium lineage hyperdisseminates to systemic sites in mice compared to gastroenteritis-associated lineages. They demonstrate that pseudogenization of a single gene, sseI, contributes to hyperdissemination of ST313 isolates via infected DCs.


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