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Deciphering interplay between Salmonella invasion effectors.

Robert J Cain1, Richard D Hayward, Vassilis Koronakis

  • 1University of Cambridge, Department of Pathology, Cambridge, United Kingdom.

Plos Pathogens
|April 5, 2008
PubMed
Summary
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Salmonella bacteria use a type III secretion system (T3SS) to inject proteins into host cells. New research reveals complex interactions between these injected proteins, uncovering a sophisticated bacterial invasion signaling network.

Area of Science:

  • Microbiology
  • Cell Biology
  • Bacterial Pathogenesis

Background:

  • Bacterial pathogens utilize specialized secretion systems, like the type III secretion system (T3SS), to deliver virulence factors into host cells.
  • Salmonella employs multiple effector proteins that individually modulate host cell actin dynamics, crucial for invasion of non-phagocytic cells.

Purpose of the Study:

  • To systematically investigate the functional interplay and crosstalk between different Salmonella T3SS effector proteins within the host cell.
  • To elucidate the signaling network governing Salmonella entry and identify synergistic and antagonistic relationships among effectors.

Main Methods:

  • Development and application of trans and cis-binary entry effector interplay (BENEFIT) screens.
  • Systematic examination of functional associations between six key Salmonella invasion effectors (SipC, SipA, SopE/2, SopB, SptP) upon co-delivery into host cells.

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Main Results:

  • Discovery of extensive, ordered synergistic and antagonistic relationships between Salmonella invasion effectors.
  • Quantification of the relative potency of these effector interactions.
  • Illumination of a complex signaling network governing bacterial entry, shaped by pathogen-host co-evolution.

Conclusions:

  • Salmonella invasion involves a highly sophisticated and coordinated network of effector protein interactions, not just individual actions.
  • The observed effector interplay highlights a complex signaling hub at the host plasma membrane during bacterial entry.
  • These findings provide new insights into the long-standing co-evolutionary arms race between bacterial pathogens and their hosts.