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Analysis of Yersinia enterocolitica Effector Translocation into Host Cells Using Beta-lactamase Effector Fusions
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Structure of a pathogenic type 3 secretion system in action.

Julia Radics1, Lisa Königsmaier1, Thomas C Marlovits2

  • 11] Research Institute of Molecular Pathology, Vienna, Austria. [2] Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna, Austria. [3].

Nature Structural & Molecular Biology
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Summary

This study visualizes the bacterial type 3 secretion system

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Area of Science:

  • Microbiology
  • Structural Biology
  • Molecular Biology

Background:

  • Type 3 secretion systems (T3SS) are essential virulence factors in many pathogenic bacteria.
  • T3SS utilize large, syringe-like protein structures called injectisomes to deliver effector proteins into host cells.
  • Understanding the mechanism of protein transport through injectisomes is crucial for developing novel antibacterial strategies.

Purpose of the Study:

  • To elucidate the requirements for substrate translocation through the Salmonella Typhimurium injectisome.
  • To visualize the injectisome in action and understand the structural basis of effector protein transport.
  • To investigate the potential for manipulating T3SS function by trapping substrates.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine the structure of the injectisome and define the secretion pathway.
  • Engineered substrates were designed to become trapped within the secretion apparatus.
  • In situ visualization techniques were employed to observe injectisomes during secretion.

Main Results:

  • The study defined the complete protein secretion path within the injectisome, from bacterial cytoplasm to host cell.
  • A structural explanation was provided for the necessity of effector protein unfolding during transport.
  • Trapping of a non-native substrate within the injectisome needle blocked the secretion of native bacterial effectors.
  • The findings demonstrated that substrate selection mechanisms can be bypassed and effector secretion inhibited.

Conclusions:

  • The research provides unprecedented structural insights into the multi-membrane protein transport mechanism of T3SS.
  • The study highlights the potential for developing T3SS inhibitors by targeting substrate translocation.
  • This work opens new avenues for understanding and combating bacterial infections mediated by T3SS.