Deciphering Interplay between Salmonella Invasion Effectors

Robert J Cain,Richard D Hayward,Vassilis Koronakis,Ralph R Isberg

doi:10.1371/journal.ppat.1000037

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.

Highlights

Many bacterial pathogens employ type III secretion systems (T3SSs) to deliver virulence effector proteins directly into eukaryotic host cells [1]
We have previously demonstrated that Salmonella entry effectors localize to the target cell plasma membrane both when expressed individually in cultured cells and after delivery via the bacterial T3SS, and we proposed the plasma membrane as a critical interface for Salmonella effector action [19]
To investigate the subcellular localization of effectors delivered by the invasion-associated Salmonella T3SS [19], we generated a Critical to the onset of Salmonella infection is the ability of bacteria to force their own entry (‘invade’) into intestinal cells of their mammalian host from where they replicate, spread and cause damage

Summary

Introduction

Many bacterial pathogens employ type III secretion systems (T3SSs) to deliver virulence effector proteins directly into eukaryotic host cells [1]. In addition to its role in effector delivery, discrete SipC domains nucleate actin polymerization and bundle actin filaments (F-actin) [7]. Both these SipC-directed activities are stimulated by SipA [8], which itself binds and stabilizes F-actin and suppresses actin turnover by host ADF/cofilin and gelsolin [9,10]. Further effectors stimulate Rho-family GTPase signaling to induce cytoskeletal and nuclear responses [11].

Methods

Results

Conclusion