Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells

Micah J. Worley, George S. Nieman, Kaoru Geddes, Fred Heffron

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

The mammalian host has a number of innate immune mechanisms designed to limit the spread of infection, yet many bacteria, including Salmonella, can cause systemic disease. Salmonella typhimurium-infected phagocytes traverse the gastrointestinal (GI) epithelium and enter the bloodstream within minutes after ingestion, thereby spreading throughout its host. Here, we provide a cellular and molecular basis for this phenomenon. We demonstrate that S. typhimurium manipulates the migratory properties of infected GI phagocytes with a type III secretion system. We show that one secreted effector, SrfH, interacts with the host protein TRIP6, a member of the zyxin family of adaptor proteins that regulate motility. SrfH promotes phagocyte motility in vitro and accelerates the systemic spread of infection away from the lumen of the intestine in the mouse. This is a previously uncharacterized mechanism by which an intracellular pathogen overcomes host defenses designed to immobilize infected cells.

Original languageEnglish (US)
Pages (from-to)17915-17920
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number47
DOIs
StatePublished - Nov 21 2006
Externally publishedYes

Keywords

  • Bacteremia
  • Secreted effector
  • TRIP6
  • Type 3 secretion
  • Virulence

ASJC Scopus subject areas

  • General

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