Abstract
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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•ST313 S. Typhimurium isolate D23580 hyperdisseminates to systemic sites in mice•ST313 isolate D23580 infects a higher number of CD11b+ migratory DCs in the MLN•ST313 isolate D23580 requires CCR7-dependent migration of DCs to hyperdisseminate•Pseudogenization of sseI in the ST313 lineage contributes to hyperdissemination
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.