deciphering interplay between salmonella invasion effectors破译沙门氏菌入侵效应器之间的相互作用.pdf

Deciphering Interplay between Salmonella Invasion Effectors Robert J. Cain.¤, Richard D. Hayward., Vassilis Koronakis* University of Cambridge, Department of Pathology, Cambridge, United Kingdom Abstract 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 cis binary 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. Citation: Cain RJ, Hayward RD, Koronakis V (2008) Deciphering Interplay between Salmonella Invasion Effectors. PLoS Pathog 4(4): e1000037. doi:10.1371/ journal.ppat.1000037 Editor: Ralph R. Isberg, Tufts University School of Medicine, United States of America Received December 13, 2007; Accepted March 3, 2008; Published April 4, 2008 Copyright: 2008 Cain et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Wellcome Trust Programme g