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A Vibrio effector protein is an inositol phosphatase and disrupts host cell membrane integrity

Christopher A Broberg1, Lingling Zhang, Herman Gonzalez

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Science (New York, N.Y.)
|August 21, 2010
PubMed

Insights

Vibrio parahaemolyticus uses effector VPA0450 to disrupt human cell membranes, causing cell death. This bacterial protein alters inositol signaling, impacting membrane integrity and host cell functions.

Area of Science:

  • Microbiology and Molecular Biology
  • Cell Biology
  • Pathogen-Host Interactions

Background:

  • Vibrio parahaemolyticus is a marine bacterium causing human gastroenteritis.
  • Type III effector proteins are virulence factors used by bacteria to manipulate host cells.
  • VPA0450 is a type III effector protein from V. parahaemolyticus implicated in host cell damage.

Purpose of the Study:

  • To elucidate the molecular mechanism by which VPA0450 contributes to host cell death.
  • To investigate the enzymatic activity and cellular targets of VPA0450.

Main Methods:

  • Biochemical assays to determine the enzymatic activity of VPA0450.
  • Cell-based assays using human cells to observe the effects of VPA0450.
  • Microscopy to analyze membrane integrity and cytoskeletal changes.

Main Results:

  • VPA0450 was identified as an inositol polyphosphate 5-phosphatase.
  • VPA0450 hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) at the D5 phosphate.
  • This enzymatic activity disrupts cytoskeletal binding sites, leading to plasma membrane blebbing, compromised integrity, and cell lysis.

Conclusions:

  • Bacterial pathogens can subvert host cell processes by targeting membrane-bound inositol signaling molecules.
  • VPA0450's activity on PIP2 disrupts membrane-cytoskeleton dynamics, contributing to Vibrio parahaemolyticus pathogenesis.
  • Understanding these mechanisms offers insights into bacterial virulence and potential therapeutic targets.

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