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

Sarah E. Carden, Gregory T. Walker, Jared Honeycutt, Kyler Lugo, Trung Pham, Amanda Jacobson, Donna Bouley, Juliana Idoyaga, Renee M Tsolis, Denise Monack

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)182-194
Number of pages13
JournalCell Host and Microbe
Volume21
Issue number2
DOIs
StatePublished - Feb 8 2017

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Keywords

  • evolution
  • genome degradation
  • iNTS
  • niche adaptation
  • nontyphoidal Salmonella
  • NTS
  • pathogenesis
  • pseudogene
  • SrfH
  • T3SS effectors

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology and Microbiology(all)
  • Cancer Research

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