Deciphering interplay between Salmonella invasion effectors.
Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a 'signaling hub' during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cisbinary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen-host interaction.
Cain
Robert J
RJ
University of Cambridge, Department of Pathology, Cambridge, United Kingdom.
Hayward
Richard D
RD
Koronakis
Vassilis
V
D000199:Actins / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002462:Cell Membrane; D003599:Cytoskeleton / Q000378:metabolism; D054884:Host-Pathogen Interactions; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells / Q000378:metabolism / Q000382:microbiology*; D010716:Phosphatidylinositols / Q000032:analysis / Q000378:metabolism; D012486:Salmonella typhimurium / Q000166:cytology / Q000378:metabolism / Q000472:pathogenicity*; D015398:Signal Transduction / Q000502:physiology
D000199:Actins; D001426:Bacterial Proteins; C111922:Cacybp protein, mouse; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D010716:Phosphatidylinositols