Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells.
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.
Worley
Micah J
MJ
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Nieman
George S
GS
Geddes
Kaoru
K
Heffron
Fred
F
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000166:cytology / Q000382:microbiology*; D060588:LIM Domain Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010586:Phagocytes / Q000382:microbiology*; D046988:Proteasome Endopeptidase Complex; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012481:Salmonella Infections, Animal; D012486:Salmonella typhimurium / Q000472:pathogenicity / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D018821:CD18 Antigens; D060588:LIM Domain Proteins; D008565:Membrane Proteins; C092282:PSMC5 protein, human; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities